Publications | Theragnostic Imaging

Can 177Lu-DOTATATE Kidney Absorbed Doses be Predicted from Pretherapy SSTR PET? Findings from Multicenter Data

Thu, 22 May 2025 00:00:00 +0000

Before performing ¹⁷⁷Lu-DOTATATE therapy for neuroendocrine tumors, somatostatin receptor (SSTR) PET imaging is currently used to confirm sufficient tumor SSTR expression, but it also has potential to be used to personalize treatment by predicting absorbed doses to critical organs. This study aims to validate the predictive capability of SSTR PET in anticipating renal absorbed dose in the first cycle of ¹⁷⁷Lu-DOTATATE using a multicenter dataset to analyze and derive insights from a broader patient population.

Methods: Retrospective data from 5 centers were included in this study: 1 in Canada (n = 25), 1 in Norway (n = 75), 1 in Sweden (n = 18), and 2 in the United States (n = 36 and n = 26). At each center, pretherapy SSTR PET/CT imaging and postcycle 1 ¹⁷⁷Lu imaging-based dosimetry were performed according to site-specific protocols. The mixed-effects model treating centers as random effects was developed using baseline SSTR PET renal uptake values to predict renal absorbed dose from ¹⁷⁷Lu-DOTATATE. Additionally, leave-one-center-out cross-validation and leave-one-sample-out cross-validation were implemented for external and internal validation, respectively, measuring mean absolute error and mean relative absolute error.

Results: Across all participating centers, the median cycle 1 renal absorbed dose was 0.56 Gy/GBq (range, 0.14-1.27 Gy/GBq), whereas the median pretherapy SSTR PET renal uptake was 110.7 Bq/mL/MBq (range, 28.6-287.7 Bq/mL/MBq). The differences among center means were statistically significant for both absorbed dose and PET uptake (P < 0.0001 from 1-way ANOVA). A significant (P < 0.05) correlation was observed between kidney SSTR PET uptake and ¹⁷⁷Lu-DOTATATE absorbed dose for each center (center-specific coefficient of determination ranged from 0.14 to 0.53). When data across all centers were aggregated, the mixed-effects model achieved a coefficient of determination of 0.25 (P < 0.01), resulting in an mean absolute error of 0.15 Gy/GBq (SD, 0.11 Gy/GBq) and an mean relative absolute error of 28% (SD, 24%) for external validation and 0.12 Gy/GBq (SD, 0.10 Gy/GBq) and 22% (SD, 20%) for internal validation.

Conclusion: The correlations observed between SSTR PET renal uptake and ¹⁷⁷Lu-DOTATATE absorbed dose to kidneys across a multicenter population are statistically significant yet modest. The prediction model achieved a mean relative absolute error 28% or less for both external and internal validation of PET-predicted absorbed doses. The intercenter differences suggest the need for standardized imaging protocols and dosimetry workflows.

Rethinking Dosimetry: A European Perspective

Thu, 22 May 2025 00:00:00 +0000

Radiopharmaceutical therapy (RPT) is entering a new era of personalization, driven by advances in molecular imaging, radiopharmaceutical development, and a growing body of clinical evidence linking absorbed dose to treatment outcomes. Although external-beam radiotherapy has long integrated dosimetry into standard practice, RPT historically relied on fixed radiopharmaceutical activities and absorbed dose-effect relationships adapted from external-beam radiotherapy, often without accounting for the unique pharmacokinetics, absorbed dose rate dynamics, and biologic responses of systemically administered radiopharmaceuticals. As RPT expands into earlier disease stages, at which patients have longer life expectancies and better performance status, the role of dosimetry in optimizing treatment is becoming increasingly evident. However, despite growing recognition of its benefits, the implementation of dosimetry in clinical practice remains limited, partly because of a self-reinforcing cycle in which the lack of routine dosimetry limits clinical evidence, which in turn hinders its broader adoption. Breaking this cycle is essential to advancing RPT and ensuring that evaluation of dosimetry is based on clinical merit rather than logistic constraints. This article examines the current landscape of RPT dosimetry, highlighting key challenges and opportunities from a European perspective and aiming to foster a more factual and constructive discussion on the topic. We discuss the fundamental differences between dosimetry-driven treatment planning and posttherapy absorbed dose verification, emphasizing the latter as a practical entry point for clinical adoption. We underscore the need for harmonized standards, improved imaging resolution, and tailored absorbed dose-effect relationships that reflect the heterogeneity of RPT delivery and the complexity of tumor and organ responses. The paper also addresses regulatory, infrastructural, and resource barriers to RPT dosimetry implementation and highlights ongoing European initiatives to strengthen frameworks, enhance stakeholder collaboration, and integrate absorbed dose biomarkers into authorization processes and clinical decision-making. By rethinking dosimetry and promoting standardized, evidence-based approaches, the field can advance beyond fixed-activity protocols toward truly individualized RPT. However, achieving clinically feasible integration of dosimetry into routine practice requires structured efforts to generate high-quality clinical evidence and improve accessibility. Ultimately, reliable, patient-centered dosimetry has the potential to enhance therapeutic efficacy, manage toxicity more effectively, and support the long-term evolution of RPT as a cornerstone of precision oncology.

Therapeutic evaluation of [212Pb]Pb-AB001 and [177Lu]Lu-PSMA-617 in a mouse model of disseminated prostate cancer

Wed, 21 May 2025 00:00:00 +0000

Metastatic castration-resistant prostate cancer (mCRPC) frequently leads to bone and soft tissue metastases, leading to poor prognosis. The beta-emitting radioligand [¹⁷⁷Lu]Lu-PSMA-617 targets the prostate-specific membrane antigen (PSMA) and may be less efficient against micrometastatic disease. The alpha-emitting radioligand [²¹²Pb]Pb-AB001 could offer enhanced treatment by delivering high energy over a short range. This study compared the efficacy of [²¹²Pb]Pb-AB001 and [¹⁷⁷Lu]Lu-PSMA-617 in a mouse model of disseminated prostate cancer. Binding and internalisation of radioligands were evaluated in PC-3 PIP-luc cells. A mouse model was established by intracardiac injection of these cells. Treatments with 0.24‒1.0 MBq [²¹²Pb]Pb-AB001 or 22‒66 MBq [¹⁷⁷Lu]Lu-PSMA-617 were initiated 7 d post-cell inoculation. Metastatic burden was measured using bioluminescence imaging, and PSMA-targeted uptake was determined with [¹⁸F]F-PSMA-1007 µPET/µCT. Gamma-autoradiography evaluated [²¹²Pb]Pb-AB001 distribution, and bone metastases were identified by radiography. Both radioligands displayed comparable in vitro binding. In vivo studies revealed metastatic formation in clinically relevant organs. µPET/µCT demonstrated increased [¹⁸F]F-PSMA-1007 uptake in metastases, matching the bioluminescence imaging results. Focal [²¹²Pb]Pb-AB001 distribution in the metastatic xenograft indicated heterogeneously distributed micrometastases in the organs. A median survival up to 47 d was achieved with [²¹²Pb]Pb-AB001, compared to 25 d for controls and 27 d for [¹⁷⁷Lu]Lu-PSMA-617. An activity-dependent reduction in bone metastases was observed for [¹⁷⁷Lu]Lu-PSMA-617, while no bone lesions were detected in [²¹²Pb]Pb-AB001-treated mice. [²¹²Pb]Pb-AB001 showed significant efficacy against micrometastases and advantages over [¹⁷⁷Lu]Lu-PSMA-617 in preventing or treating early bone metastases for the investigated injected activities. This implies clinical potential for treating mCRPC, including patients at risk of early metastatic disease, but further studies including dosimetry and toxicity analyses are required with regards to activity levels.

First-in-Human Phase 0 Study of AB001, a Prostate-Specific Membrane Antigen-Targeted 212Pb Radioligand, in Patients with Metastatic Castration-Resistant Prostate Cancer

Thu, 01 May 2025 00:00:00 +0000

AB001, a prostate-specific membrane antigen (PSMA)-targeted small molecule labeled with the in vivo-generating α-emitter ²¹²Pb, was investigated in a phase 0 trial in patients with metastatic castration-resistant prostate cancer (mCRPC). The primary objective was to explore the feasibility of γ-camera imaging to assess biodistribution and uptake in metastatic lesions.

Methods: Three patients with progressive mCRPC and Eastern Cooperative Oncology Group performance status 1 were included, having prostate-specific antigen levels of 0.44, 0.75, and 15 µg/L. All had at least 3 PSMA-expressing metastatic lesions, with an SUV_max range of 10.1-77.4 on PSMA PET. Each patient received a microdose of 9.4 ± 0.3 MBq of AB001 intravenously. Planar γ-camera and SPECT/CT imaging was scheduled 1-3 h and 16-24 h after administration. Whole-body clearance was assessed with NaI probe measurements. Activity of ²¹²Pb in whole blood and plasma was measured to investigate clearance from blood and in vivo stability of the ligand. Safety, tolerability, and efficacy biomarkers (prostate-specific antigen, alkaline phosphatase) were followed for 28 d.

Results: AB001 uptake in the lesion with the highest PSMA expression, a retrocaval lymph node metastasis with a short-axis diameter of 11 mm, was visualized on SPECT. Uptake of AB001 was not clearly demonstrated for other metastatic lesions, possibly because of the lower PSMA expression of these metastases on PSMA PET, combined with the administered AB001 microdose and imaging system limitations. Kidney, urinary bladder with contents, and liver uptake of AB001 were clearly distinguishable from adjacent tissue, and the blood pool content was seen. Salivary glands were not visualized. Blood analyses indicated stability of AB001 after injection, and whole-body probe measurements demonstrated an effective half-life of 8 h. There were no complications related to injection of AB001 or adverse reactions during follow-up. As expected for a phase 0 study, there was no indication of therapeutic effects as assessed by prostate-specific antigen and alkaline phosphatase.

Conclusion: The ²¹²Pb-based radioligand AB001 was safely administered to mCRPC patients. γ-camera imaging of AB001 was feasible, even at a microdose, and demonstrated metastatic targeting, albeit for only 1 lesion. The promising biodistribution and clearance encourage further clinical investigation.

Added Value of [18F]PSMA-1007 PET/CT and PET/MRI in Patients With Biochemically Recurrent Prostate Cancer: Impact on Detection Rates and Clinical Management

Wed, 01 Jan 2025 00:00:00 +0000

Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) can change management in a large fraction of patients with biochemically recurrent prostate cancer (BCR). To investigate the added value of PET to MRI and CT for this patient group, and to explore whether the choice of the PET paired modality (PET/MRI vs. PET/CT) impacts detection rates and clinical management. Retrospective. 41 patients with BCR (median age [range]: 68 [55-78]). 3T, including T1-weighted gradient echo (GRE), T2-weighted turbo spin echo (TSE) and dynamic contrast-enhanced GRE sequences, diffusion-weighted echo-planar imaging, and a T1-weighted TSE spine sequence. In addition to MRI, [¹⁸F]PSMA-1007 PET and low-dose CT were acquired on the same day. Images were reported using a five-point Likert scale by two teams each consisting of a radiologist and a nuclear medicine physician. The radiologist performed a reading using CT and MRI data and a joint reading between radiologist and nuclear medicine physician was performed using MRI, CT, and PET from either PET/MRI or PET/CT. Findings were presented to an oncologist to create intended treatment plans. Intrareader and interreader agreement analysis was performed. McNemar test, Cohen’s κ, and intraclass correlation coefficients. A P-value <0.05 was considered significant. 7 patients had positive findings on MRI and CT, 22 patients on joint reading with PET/CT, and 18 patients joint reading with PET/MRI. For overall positivity, interreader agreement was poor for MR and CT (κ = 0.36) and almost perfect with addition of PET (PET/CT κ = 0.85, PET/MRI κ = 0.85). The addition of PET from PET/CT and PET/MRI changed intended treatment in 20 and 18 patients, respectively. Between joint readings, intended treatment was different for eight patients. The addition of [¹⁸F]PSMA-1007 PET/MRI or PET/CT to MRI and CT may increase detection rates, could reduce interreader variability, and may change intended treatment in half of patients with BCR. 3 TECHNICAL EFFICACY: Stage 3.

Outcome prediction based on [18F]FDG PET/CT in patients with pleural mesothelioma treated with ipilimumab and nivolumab +/- UV1 telomerase vaccine

Wed, 01 Jan 2025 00:00:00 +0000

The introduction of immunotherapy in pleural mesothelioma (PM) has highlighted the need for effective outcome predictors. This study explores the role of [18F]FDG PET/CT in predicting outcomes in PM treated with immunotherapy. Patients from the NIPU trial, receiving ipilimumab and nivolumab +/- telomerase vaccine in second-line, were included. [18F]FDG PET/CT was obtained at baseline (n = 100) and at week-5 (n = 76). Metabolic tumour volume (MTV) and peak standardised uptake value (SUV_peak) were evaluated in relation to survival outcomes. Wilcoxon rank-sum test was used to assess differences in MTV, total lesion glycolysis (TLG), maximum standardised uptake value (SUV_max) and SUV_peak between patients exhibiting an objective response, defined as either partial response or complete response according to the modified Response Criteria in Solid Tumours (mRECIST) and immune RECIST (iRECIST), and non-responders, defined as either stable disease or progressive disease as their best overall response. Univariate Cox regression revealed significant associations of MTV with OS (HR 1.36, CI: 1.14, 1.62, p < 0.001) and PFS (HR 1.18, CI: 1.03, 1.34, p = 0.02), while multivariate analysis showed a significant association with OS only (HR 1.35, CI: 1.09, 1.68, p = 0.007). While SUV_peak was not significantly associated with OS or PFS in univariate analyses, it was significantly associated with OS in multivariate analysis (HR 0.43, CI: 0.23, 0.80, p = 0.008). Objective responders had significant reductions in TLG, SUV_max and SUV_peak at week-5. MTV provides prognostic value in PM treated with immunotherapy. High SUV_peak was not associated with inferior outcomes, which could be attributed to the distinct mechanisms of immunotherapy. Early reductions in PET metrics correlated with treatment response. The NIPU trial (NCT04300244) is registered at clinicaltrials.gov. https://classic. gov/ct2/show/NCT04300244?cond=Pleural+Mesothelioma&cntry=NO&draw=2&rank=4.

The prognostic value of [18F]FDG PET/CT texture analysis prior to transplantation for unresectable colorectal liver metastases

Wed, 01 Jan 2025 00:00:00 +0000

To determine whether heterogeneity in colorectal liver metastases (CRLM) ¹⁸F fluorodeoxyglucose [¹⁸F]FDG distribution is predictive of disease-free survival (DFS) and overall survival (OS) following liver transplantation (LT) for unresectable CRLM. The preoperative [¹⁸F]FDG positron emission tomography/computed tomography examinations of all patients in the secondary cancer 1 and 2 studies were retrospectively assessed. Maximum standardized uptake value (SUV_max), metabolic tumour volume (MTV), and six texture heterogeneity parameters (joint entropy_GLCM, dissimilarity_GLCM, grey level variance_SZM, size zone variance_SZM, and zone percentage_SZM, and morphological feature convex deficiency) were obtained. DFS and OS for patients over and under the median value for each of these parameters were compared by using the Kaplan Meier method and log rank test. Twenty-eight out of 40 patients who underwent LT for unresectable CRLM had liver metastases with uptake above liver background and were eligible for inclusion. Low MTV (p < 0.001) and dissimilarity_GLCM (p = 0.016) were correlated to longer DFS. Low MTV (p < 0.001) and low values of the texture parameters dissimilarity_GLCM (p = 0.038), joint entropy_GLCM (p = 0.015) and zone percentage_SZM (p = 0.037) were significantly correlated to longer OS. SUV_max was not correlated to DFS and OS. Although some texture parameters were able to significantly predict DFS and OS, MTV seems to be superior to predict both DFS and OS following LT for unresectable CRLM.

Do we need dosimetry for the optimization of theranostics in CNS tumors?

Mon, 09 Dec 2024 00:00:00 +0000

Radiopharmaceutical theranostic treatments have grown exponentially worldwide, and internal dosimetry has attracted attention and resources. Despite some similarities with chemotherapy, radiopharmaceutical treatments are essentially radiotherapy treatments, as the release of radiation into tissues is the determinant of the observed clinical effects. Therefore, absorbed dose calculations are key to explaining dose-effect correlations and individualizing radiopharmaceutical treatments. The present article introduces the basic principles of internal dosimetry and provides an overview of available loco-regional and systemic radiopharmaceutical treatments for central nervous system (CNS) tumors. The specific characteristics of dosimetry as applied to these treatments are highlighted, along with their limitations and most relevant results. Dosimetry is performed with higher precision and better reproducibility than in the past, and dosimetric data should be systematically collected, as treatment planning and verification may help exploit the full potential of theranostic of CNS tumors.

Twisted clustered pinhole collimation for improved high-energy preclinical SPECT/PET

Wed, 13 Nov 2024 00:00:00 +0000

Objective.Advanced pinhole collimation geometries optimized for preclinical high-energyɣimaging facilitate applications such asɑandßemitter imaging, simultaneous multi-isotope PET and PET/SPECT, and positron range-free PET. These geometries replace each pinhole with a group of clustered pinholes (CPs) featuring smaller individual pinhole opening angles (POAs), enabling sub-mm resolution imaging up to ∼1 MeV. Further narrowing POAs while retaining field-of-view (FOV) may enhance high-energy imaging but faces geometrical constraints. Here, we detail how the novel twisted CPs (TCPs) address this challenge.*Approach.*We compared TCP and CP collimator sensitivity at equal system resolution (SR) and SR at matched sensitivity by tuning pinhole diameters for¹⁸F (511 keV) and⁸⁹Zr (909 keV). Additionally, simulated Derenzo phantoms at low activity (LA: 12 MBq ml^-1) and high activity (HA: 190 MBq ml^-1) levels, along with uniformity images, were compared to assess image resolution and uniformity.*Main results.*At equal SR, TCP increased average central FOV sensitivity by 15.6% for¹⁸F and 29.4% for⁸⁹Zr compared to CP. Image resolution was comparable, except for⁸⁹Zr at LA, where TCP resolved 0.80 mm diameter rods compared to 0.90 mm for CP. Image uniformity was equivalent for¹⁸F, while for⁸⁹Zr TCP granted a 10.4% improvement. For collimators with matched sensitivity, TCP improved SR by 6.6% for¹⁸F and 17.7% for⁸⁹Zr while also enhancing image resolution; for¹⁸F, rods distinguished were 0.65 mm (CP) and 0.60 mm (TCP) for HA, and 0.70 mm (CP and TCP) for LA. For⁸⁹Zr, image resolutions were 0.75 mm (CP) and 0.65 mm (TCP) for HA, and 0.90 mm (CP) and 0.80 mm (TCP) for LA. Image uniformity with TCP decreased by 18.3% for¹⁸F but improved by 20.1% for⁸⁹Zr.Significance.This study suggests that the TCP design has potential to improve high-energyɣimaging.

SPECT/CT Image-Derived Absorbed Dose to Red Marrow Correlates with Hematologic Toxicity in Patients Treated with [177Lu]Lu-DOTATATE

Wed, 01 May 2024 00:00:00 +0000

Hematologic toxicity, although often transient, is the most common limiting adverse effect during somatostatin peptide receptor radionuclide therapy. This study investigated the association between Monte Carlo-derived absorbed dose to the red marrow (RM) and hematologic toxicity in patients being treated for their neuroendocrine tumors.

Methods: Twenty patients each receiving 4 treatment cycles of [¹⁷⁷Lu]Lu-DOTATATE were included. Multiple-time-point ¹⁷⁷Lu SPECT/CT imaging-based RM dosimetry was performed using an artificial intelligence-driven workflow to segment vertebral spongiosa within the field of view (FOV). This workflow was coupled with an in-house macroscale/microscale Monte Carlo code that incorporates a spongiosa microstructure model. Absorbed dose estimates to RM in lumbar and thoracic vertebrae within the FOV, considered as representations of the whole-body RM absorbed dose, were correlated with hematologic toxicity markers at about 8 wk after each cycle and at 3- and 6-mo follow-up after completion of all cycles.

Results: The median of absorbed dose to RM in lumbar and thoracic vertebrae within the FOV (D _{median,vertebrae}) ranged from 0.019 to 0.11 Gy/GBq. The median of cumulative absorbed dose across all 4 cycles was 1.3 Gy (range, 0.6-2.5 Gy). Hematologic toxicity was generally mild, with no grade 2 or higher toxicity for platelets, neutrophils, or hemoglobin. However, there was a decline in blood counts over time, with a fractional value relative to baseline at 6 mo of 74%, 97%, 57%, and 97%, for platelets, neutrophils, lymphocytes, and hemoglobin, respectively. Statistically significant correlations were found between a subset of hematologic toxicity markers and RM absorbed doses, both during treatment and at 3- and 6-mo follow-up. This included a correlation between the platelet count relative to baseline at 6-mo follow up: D _{median,vertebrae} (r = -0.64, P = 0.015), D _{median,lumbar} (r = -0.72, P = 0.0038), D _{median,thoracic} (r = -0.58, P = 0.029), and D _{average,vertebrae} (r = -0.66, P = 0.010), where D _{median,lumbar} and D _{median,thoracic} are median absorbed dose to the RM in the lumbar and thoracic vertebrae, respectively, within the FOV and D _{average,vertebrae} is the mass-weighted average absorbed dose of all vertebrae.

Conclusion: This study found a significant correlation between image-derived absorbed dose to the RM and hematologic toxicity, including a relative reduction of platelets at 6-mo follow up. These findings indicate that absorbed dose to the RM can potentially be used to understand and manage hematologic toxicity in peptide receptor radionuclide therapy.

EANM guidance document: dosimetry for first-in-human studies and early phase clinical trials

Mon, 01 Apr 2024 00:00:00 +0000

The numbers of diagnostic and therapeutic nuclear medicine agents under investigation are rapidly increasing. Both novel emitters and novel carrier molecules require careful selection of measurement procedures. This document provides guidance relevant to dosimetry for first-in human and early phase clinical trials of such novel agents. The guideline includes a short introduction to different emitters and carrier molecules, followed by recommendations on the methods for activity measurement, pharmacokinetic analyses, as well as absorbed dose calculations and uncertainty analyses. The optimal use of preclinical information and studies involving diagnostic analogues is discussed. Good practice reporting is emphasised, and relevant dosimetry parameters and method descriptions to be included are listed. Three examples of first-in-human dosimetry studies, both for diagnostic tracers and radionuclide therapies, are given.

Implementation of dosimetry for molecular radiotherapy; results from a European survey

Mon, 01 Jan 2024 00:00:00 +0000

The use of molecular radiotherapy (MRT) has been rapidly evolving over the last years. The aim of this study was to assess the current implementation of dosimetry for MRTs in Europe. A web-based questionnaire was open for treating centres between April and June 2022, and focused on 2020-2022. Questions addressed the application of 16 different MRTs, the availability and involvement of medical physicists, software used, quality assurance, as well as the target regions for dosimetry, whether treatment planning and/or verification were performed, and the dosimetric methods used. A total of 173 responses suitable for analysis was received from centres performing MRT, geographically distributed over 27 European countries. Of these, 146 centres (84 %) indicated to perform some form of dosimetry, and 97 % of these centres had a medical physicist available and almost always involved in dosimetry. The most common MRTs were ¹³¹I-based treatments for thyroid diseases and thyroid cancer, and [²²³Ra]RaCl₂ for bone metastases. The implementation of dosimetry varied widely between therapies, from almost all centres performing dosimetry-based planning for microsphere treatments to none for some of the less common treatments (like ³²P sodium-phosphate for myeloproliferative disease and [⁸⁹Sr]SrCl₂ for bone metastases). Over the last years, implementation of dosimetry, both for pre-therapeutic treatment planning and post-therapy absorbed dose verification, increased for several treatments, especially for microsphere treatments. For other treatments that have moved from research to clinical routine, the use of dosimetry decreased in recent years. However, there are still large differences both across and within countries.

Time-Activity data fitting in molecular Radiotherapy: Methodology and pitfalls

Mon, 01 Jan 2024 00:00:00 +0000

Absorbed radiation doses are essential in assessing the effects, e.g. safety and efficacy, of radiopharmaceutical therapy (RPT). Patient-specific absorbed dose calculations in the target or the organ at risk require multiple inputs. These include the number of disintegrations in the organ, i.e. the time-integrated activities (TIAs) of the organs, as well as other parameters describing the process of radiation energy deposition in the target tissue (i.e. mean energy per disintegration, radiation dose constants, etc). TIAs are then estimated by incorporating the area under the radiopharmaceutical’s time-activity curve (TAC), which can be obtained by quantitative measurements of the biokinetics in the patient (typically based on imaging data such as planar scintigraphy, SPECT/CT, PET/CT, or blood and urine samples). The process of TAC determination/calculation for RPT generally depends on the user, e.g., the chosen number and schedule of measured time points, the selection of the fit function, the error model for the data and the fit algorithm. These decisions can strongly affect the final TIA values and thus the accuracy of calculated absorbed doses. Despite the high clinical importance of the TIA values, there is currently no consensus on processing time-activity data or even a clear understanding of the influence of uncertainties and variations in personalised RPT dosimetry related to user-dependent TAC calculation. As a first step towards minimising site-dependent variability in RPT dosimetry, this work provides an overview of quality assurance and uncertainty management considerations of the TIA estimation.

EFOMP policy statement NO. 19: Dosimetry in nuclear medicine therapy - Molecular radiotherapy

Fri, 01 Dec 2023 00:00:00 +0000

The European Council Directive 2013/59/Euratom (BSS Directive) includes optimisation of treatment with radiotherapeutic procedures based on patient dosimetry and verification of the absorbed doses delivered. The present policy statement summarises aspects of three directives relating to the therapeutic use of radiopharmaceuticals and medical devices, and outlines the steps needed for implementation of patient dosimetry for radioactive drugs. To support the transition from administrations of fixed activities to personalised treatments based on patient-specific dosimetry, EFOMP presents a number of recommendations including: increased networking between centres and disciplines to support data collection and development of codes-of-practice; resourcing to support an infrastructure that permits routine patient dosimetry; research funding to support investigation into individualised treatments; inter-disciplinary training and education programmes; and support for investigator led clinical trials. Close collaborations between the medical physicist and responsible practitioner are encouraged to develop a similar pathway as is routine for external beam radiotherapy and brachytherapy. EFOMP’s policy is to promote the roles and responsibilities of medical physics throughout Europe in the development of molecular radiotherapy to ensure patient benefit. As the BSS directive is adopted throughout Europe, unprecedented opportunities arise to develop informed treatments that will mitigate the risks of under- or over-treatments.

Traceable calibration with 177Lu and comparison of activity meters at hospitals in Norway and Sweden

Fri, 01 Dec 2023 00:00:00 +0000

The activity meter is used to determine the activity of delivered radiopharmaceuticals, administered activity to patients and reference activity when gamma-cameras are calibrated prior to imaged-based dosimetry. The aim is to describe a procedure for cross-calibration of activity meters at different clinical sites, and report on ¹⁷⁷Lu activity results when using factory-set calibration factors compared to when calibration is performed with traceability to a primary standard. Thirty activity meters placed at seven hospitals in Norway and Sweden from four manufacturers: Capintec, Commecer, NuviaTech and Veenstra were included. A stock solution with ¹⁷⁷Lu was prepared at the local sites and measured in each activity meter with factory settings. The solution was shipped to the reference site at Lund University for measurements in a secondary standard activity meter. Deviations between local and reference activity measurements were determined for three geometries: 25-mL vial, 10-mL syringe and 1-mL syringe. The median of the deviations was 6.4 % for the 25 mL vial, 5.9 % for the 10 mL syringe and 6.8 % for the 1 mL syringe. The median of the deviations for the 25 mL vial, was 1.5 % for activity meters from Capintec, 7.0 % for Comecer, 11.0 % for NuviaTech and 2.4 % for Veenstra. The majority of the deviations were positive and the maximum deviation was 14.5 %. The activity of ¹⁷⁷Lu measured in an activity meter with factory-set dial settings may yield deviations up to 14.5%, compared to activities measured with traceability to a primary standard. This would imply an undertreatment of patients.

New nuclear medicine diagnostic method for parathyroid

Mon, 27 Nov 2023 00:00:00 +0000

No abstract available

Use of ionizing radiation in a Norwegian cohort of children with congenital heart disease: imaging frequency and radiation dose for the Health Effects of Cardiac Fluoroscopy and Modern Radiotherapy in Pediatrics (HARMONIC) study

Wed, 01 Nov 2023 00:00:00 +0000

The European-funded Health Effects of Cardiac Fluoroscopy and Modern Radiotherapy in Pediatrics (HARMONIC) project is a multicenter cohort study assessing the long-term effects of ionizing radiation in patients with congenital heart disease. Knowledge is lacking regarding the use of ionizing radiation from sources other than cardiac catheterization in this cohort. This study aims to assess imaging frequency and radiation dose (excluding cardiac catheterization) to patients from a single center participating in the Norwegian HARMONIC project. Between 2000 and 2020, we recruited 3,609 patients treated for congenital heart disease (age < 18 years), with 33,768 examinations categorized by modality and body region. Data were retrieved from the radiology information system. Effective doses were estimated using International Commission on Radiological Protection Publication 60 conversion factors, and the analysis was stratified into six age categories: newborn; 1 year, 5 years, 10 years, 15 years, and late adolescence. The examination distribution was as follows: 91.0% conventional radiography, 4.0% computed tomography (CT), 3.6% diagnostic fluoroscopy, 1.2% nuclear medicine, and 0.3% noncardiac intervention. In the newborn to 15 years age categories, 4-12% had ≥ ten conventional radiography studies, 1-8% underwent CT, and 0.3-2.5% received nuclear medicine examinations. The median effective dose ranged from 0.008-0.02 mSv and from 0.76-3.47 mSv for thoracic conventional radiography and thoracic CT, respectively. The total effective dose burden from thoracic conventional radiography ranged between 28-65% of the dose burden from thoracic CT in various age categories (40% for all ages combined). The median effective dose for nuclear medicine lung perfusion was 0.6-0.86 mSv and for gastrointestinal fluoroscopy 0.17-0.27 mSv. Because of their low frequency, these procedures contributed less to the total effective dose than thoracic radiography. This study shows that CT made the largest contribution to the radiation dose from imaging (excluding cardiac intervention). However, although the dose per conventional radiograph was low, the large number of examinations resulted in a substantial total effective dose. Therefore, it is important to consider the frequency of conventional radiography while calculating cumulative dose for individuals. The findings of this study will help the HARMONIC project to improve risk assessment by minimizing the uncertainty associated with cumulative dose calculations.

Optimization of Q.Clear reconstruction for dynamic 18F PET imaging

Fri, 20 Oct 2023 00:00:00 +0000

Q.Clear, a Bayesian penalized likelihood reconstruction algorithm, has shown high potential in improving quantitation accuracy in PET systems. The Q.Clear algorithm controls noise during the iterative reconstruction through a β penalization factor. This study aimed to determine the optimal β-factor for accurate quantitation of dynamic PET scans. A Flangeless Esser PET Phantom with eight hollow spheres (4-25 mm) was scanned on a GE Discovery MI PET/CT system. Data were reconstructed into five sets of variable acquisition times using Q.Clear with 18 different β-factors ranging from 100 to 3500. The recovery coefficient (RC), coefficient of variation (CV_RC) and root-mean-square error (RMSE_RC) were evaluated for the phantom data. Two male patients with recurrent glioblastoma were scanned on the same scanner using ¹⁸F-PSMA-1007. Using an irreversible two-tissue compartment model, the area under curve (AUC) and the net influx rate K_i were calculated to assess the impact of different β-factors on the pharmacokinetic analysis of clinical PET brain data. In general, RC and CV_RC decreased with increasing β-factor in the phantom data. For small spheres (< 10 mm), and in particular for short acquisition times, low β-factors resulted in high variability and an overestimation of measured activity. Increasing the β-factor improves the variability, however at a cost of underestimating the measured activity. For the clinical data, AUC decreased and K_i increased with increased β-factor; a change in β-factor from 300 to 1000 resulted in a 25.5% increase in the K_i. In a complex dynamic dataset with variable acquisition times, the optimal β-factor provides a balance between accuracy and precision. Based on our results, we suggest a β-factor of 300-500 for quantitation of small structures with dynamic PET imaging, while large structures may benefit from higher β-factors. Clinicaltrials.gov, NCT03951142. Registered 5 October 2019, https://clinicaltrials.gov/ct2/show/NCT03951142 . EudraCT no 2018-003229-27. Registered 26 February 2019, https://www.clinicaltrialsregister.eu/ctr-search/trial/2018-003229-27/NO .

Intensifying treatment in PET-positive multiple myeloma patients after upfront autologous stem cell transplantation

Sun, 01 Oct 2023 00:00:00 +0000

¹⁸F-Fluorodeoxyglucose positron emission tomography/computed tomography (PET) positivity after first-line treatment with autologous stem cell transplantation (ASCT) in multiple myeloma is strongly correlated with reduced progression-free and overall survival. However, PET-positive patients who achieve PET negativity after treatment seem to have comparable outcomes to patients who were PET negative at diagnosis. Hence, giving PET-positive patients additional treatment may improve their outcome. In this phase II study, we screened first-line patients with very good partial response (VGPR) or better after ASCT with PET. PET-positive patients received four 28-day cycles of carfilzomib-lenalidomide-dexamethasone (KRd). Flow cytometry-based minimal residual disease (MRD) analysis was performed before and after treatment for correlation with PET. Overall, 159 patients were screened with PET. A total of 53 patients (33%) were PET positive and 57% of PET-positive patients were MRD negative, demonstrating that these response assessments are complementary. KRd consolidation converted 33% of PET-positive patients into PET negativity. MRD-negative patients were more likely to convert than MRD-positive patients. In summary, PET after ASCT detected residual disease in a substantial proportion of patients in VGPR or better, even in patients who were MRD negative, and KRd consolidation treatment changed PET status in 33% of patients.

Imaging of 212Pb in mice with a clinical SPECT/CT

Mon, 21 Aug 2023 00:00:00 +0000

²¹²Pb is a promising radionuclide for targeted alpha therapy. Here, the feasibility of visualising the tumour uptake and biodistribution of ²¹²Pb-NG001 in mice with a clinical SPECT/CT scanner was investigated. A mouse phantom with ²¹²Pb was imaged with a clinical- and a preclinical SPECT/CT scanner. Different acquisition and reconstruction settings were investigated on the clinical system (Siemens Symbia Intevo Bold). Two athymic nude mice carrying PC-3 PIP prostate cancer tumours of 235-830 μl received 1.44 MBq of ²¹²Pb-NG001 and were imaged 2, 6, and 24 h post-injection on the clinical SPECT/CT with a Medium Energy collimator and a 40% energy window centred on 79 keV. All acquisition times were 30 min, except the mouse imaging 24 h post-injection which was 60 min. After the final imaging, the organs were harvested and measured on a gamma counter to give an indication of how much activity was present in organs of interest at the last imaging time point. Four volumes in the mouse phantom of ~ 300 μl with 246-303 kBq/ml of ²¹²Pb were distinguishable on images acquired with the clinical SPECT/CT with a high number of reconstruction updates. With the preclinical SPECT, the same volumes were easily distinguished with 49 kBq/ml of ²¹²Pb. Clinical SPECT/CT images of the mice revealed uptake in tumours and bladders 2 h after injection and in tumours containing down to approximately 15 kBq/ml at 6 and 24 h after injection. Although the preclinical scanner should be used preferentially in biodistribution studies in mice, the clinical SPECT/CT confirmed uptake in small volumes (e.g. ~ 300 μl volume with ~ 250 kBq/ml). Regardless of system, the resolution and sensitivity limits should be carefully determined, otherwise false negative or too low uptakes can be wrongly interpreted.

Correction to: EANM enabling guide: how to improve the accessibility of clinical dosimetry

Tue, 01 Aug 2023 00:00:00 +0000

No abstract available

Optimized SPECT Imaging of 224Ra α-Particle Therapy by 212Pb Photon Emissions

Sat, 01 Jul 2023 00:00:00 +0000

In preparation for an α-particle therapy trial using 1-7 MBq of ²²⁴Ra, the feasibility of tomographic SPECT/CT imaging was of interest. The nuclide decays in 6 steps to stable ²⁰⁸Pb, with ²¹²Pb as the principle photon-emitting nuclide. ²¹²Bi and ²⁰⁸Tl emit high-energy photons up to 2,615 keV. A phantom study was conducted to determine the optimal acquisition and reconstruction protocol.

Methods: The spheres of a body phantom were filled with a ²²⁴Ra-RaCl₂ solution, and the background compartment was filled with water. Images were acquired on a SPECT/CT system. In addition, 30-min scans were acquired for 80- and 240-keV emissions, using triple-energy windows, with both medium-energy and high-energy collimators. Images were acquired at 90-95 and 29-30 kBq/mL, plus an explorative 3-min acquisition at 20 kBq/mL (using only the optimal protocol). Reconstructions were performed with attenuation correction only, attenuation plus scatter correction, 3 levels of postfiltering, and 24 levels of iterative updates. Acquisitions and reconstructions were compared using the maximum value and signal-to-scatter peak ratio for each sphere. Monte Carlo simulations were performed to examine the contributions of key emissions.

Results: Secondary photons of the 2,615-keV ²⁰⁸Tl emission produced in the collimators make up most of the acquired energy spectrum, as revealed by Monte Carlo simulations, with only a small fraction (3%-6%) of photons in each window providing useful information for imaging. Still, decent image quality is possible at 30 kBq/mL, and nuclide concentrations are imageable down to approximately 2-5 kBq/mL. The overall best results were obtained with the 240-keV window, medium-energy collimator, attenuation and scatter correction, 30 iterations and 2 subsets, and a 12-mm gaussian postprocessing filter. However, all combinations of the applied collimators and energy windows were capable of producing adequate results, even though some failed to reconstruct the 2 smallest spheres.

Conclusion: SPECT/CT imaging of ²²⁴Ra in equilibrium with daughters is possible, with sufficient image quality to provide clinical utility for the current trial of intraperitoneally administrated activity. A systematic scheme for optimization was designed to select acquisition and reconstruction settings.

Results from an EANM survey on time estimates and personnel responsible for main tasks in molecular radiotherapy dosimetry

Sat, 01 Jul 2023 00:00:00 +0000

No abstract available

EANM enabling guide: how to improve the accessibility of clinical dosimetry

Thu, 01 Jun 2023 00:00:00 +0000

Dosimetry can be a useful tool for personalization of molecular radiotherapy (MRT) procedures, enabling the continuous development of theranostic concepts. However, the additional resource requirements are often seen as a barrier to implementation. This guide discusses the requirements for dosimetry and demonstrates how a dosimetry regimen can be tailored to the available facilities of a centre. The aim is to help centres wishing to initiate a dosimetry service but may not have the experience or resources of some of the more established therapy and dosimetry centres. The multidisciplinary approach and different personnel requirements are discussed and key equipment reviewed example protocols demonstrating these factors are given in the supplementary material for the main therapies carried out in nuclear medicine, including [¹³¹I]-NaI for benign thyroid disorders, [¹⁷⁷Lu]-DOTATATE and ¹³¹I-mIBG for neuroendocrine tumours and [⁹⁰Y]-microspheres for unresectable hepatic carcinoma.

Radioimmunotherapy of Non-Hodgkin B-cell Lymphoma: An update

Mon, 01 May 2023 00:00:00 +0000

Systemic radioimmunotherapy (RIT) is arguably the most effective and least toxic anticancer treatment for non-Hodgkin lymphoma (NHL). In treatment-naïve patients with indolent NHL, the efficacy of a single injection of RIT compares with that of multiple cycles of combination chemotherapy. However, 20 years following the approval of the first CD20-targeting radioimmunoconjugates ⁹⁰Y-Ibritumomab-tiuxetan (Zevalin) and ¹³¹I-tositumomab (Bexxar), the number of patients referred for RIT in western countries has dramatically decreased. Notwithstanding this, the development of RIT has continued. Therapeutic targets other than CD20 have been identified, new vector molecules have been produced allowing for faster delivery of RIT to the target, and innovative radionuclides with favorable physical characteristics such as alpha emitters have been more widely available. In this article, we reviewed the current status of RIT in NHL, with particular focus on recent clinical and preclinical developments.

Correlations between [68Ga]Ga-DOTA-TOC Uptake and Absorbed Dose from [177Lu]Lu-DOTA-TATE

Fri, 10 Feb 2023 00:00:00 +0000

The aim of this paper was to investigate correlations between pre- therapeutic [⁶⁸Ga]Ga-DOTA-TOC uptake and absorbed dose to tumours from therapy with [¹⁷⁷Lu]Lu-DOTA-TATE. This retrospective study included 301 tumours from 54 GEP-NET patients. The tumours were segmented on pre-therapeutic [⁶⁸Ga]Ga-DOTA-TOC PET/CT, and post-therapy [¹⁷⁷Lu]Lu-DOTA-TATE SPECT/CT images, using a fixed 40% threshold. The SPECT/CT images were used for absorbed dose calculations by assuming a linear build-up from time zero to day one, and mono-exponential wash-out after that. Both SUV_mean and SUV_max were measured from the PET images. A linear absorbed-dose prediction model was formed with SUV_mean as the independent variable, and the accuracy was tested with a split 70-30 training-test set. Mean SUV_mean and SUV_max from [⁶⁸Ga]Ga-DOTA-TOC PET was 24.0 (3.6-84.4) and 41.0 (6.7-146.5), and the mean absorbed dose from [¹⁷⁷Lu]Lu-DOTA-TATE was 26.9 Gy (2.4-101.9). A linear relationship between SUV_mean and [¹⁷⁷Lu]Lu-DOTA-TATE activity concentration at 24 h post injection was found (R² = 0.44, p < 0.05). In the prediction model, a root mean squared error and a mean absolute error of 1.77 and 1.33 Gy/GBq, respectively, were found for the test set. There was a high inter- and intra-patient variability in tumour measurements, both for [⁶⁸Ga]Ga-DOTA-TOC SUVs and absorbed doses from [¹⁷⁷Lu]Lu-DOTA-TATE. Depending on the required accuracy, [⁶⁸Ga]Ga-DOTA-TOC PET imaging may estimate the [¹⁷⁷Lu]Lu-DOTA-TATE uptake. However, there could be a high variance between predicted and actual absorbed doses.

Radiation safety considerations for the use of radium-224-calciumcarbonate-microparticles in patients with peritoneal metastasis

Wed, 08 Feb 2023 00:00:00 +0000

Two ongoing phase I studies are investigating the use of radium-224 adsorbed to calcium carbonate micro particles (²²⁴Ra-CaCO₃-MP) to treat peritoneal metastasis originating from colorectal or ovarian cancer. The aim of this work was to study the level of radiation exposure from the patients to workers at the hospital, carers and members of the public. Six patients from the phase 1 trial in patients with colorectal cancer were included in this study. Two days after cytoreductive surgery, they were injected with 7 MBq of ²²⁴Ra-CaCO₃-MP. At approximately 3, 24 and 120 h after injection, the patients underwent measurements with an ionization chamber and a scintillator-based iodide detector, and whole body gamma camera imaging. The patient was modelled as a planar source to calculate dose rate as a function of distance. Scenarios varying in duration and distance from the patient were created to estimate the potential effective doses from external exposure. Urine and blood samples were collected at approximately 3, 6, 24, 48 and 120 h after injection of ²²⁴Ra-CaCO₃-MP, to estimate the activity concentration of ²²⁴Ra and ²¹²Pb. The patients’ median effective whole-body half-life of ²²⁴Ra-CaCO₃-MP ranged from 2.6 to 3.5 days, with a mean value of 3.0 days. In the scenarios with exposure at the hospital (first 8 days), sporadic patient contact resulted in a range of 3.9-6.8 μSv per patient, and daily contact resulted in 4.3-31.3 μSv depending on the scenario. After discharge from the hospital, at day 8, the highest effective dose was received by those with close daily contact; 18.7-83.0 μSv. The highest activity concentrations of ²²⁴Ra and ²¹²Pb in urine and blood were found within 6 h, with maximum values of 70 Bq/g for ²²⁴Ra and 628 Bq/g for ²¹²Pb. The number of patients treated with ²²⁴Ra-CaCO₃-MP that a single hospital worker - involved in extensive care - can receive per year, before effective doses of 6 mSv from external exposure is exceeded, is in the order of 200-400. Members of the public and family members are expected to receive well below 0.25 mSv, and therefore, no restrictions to reduce external exposure should be required.

Scar imaging in the dyssynchronous left ventricle: Accuracy of myocardial metabolism by positron emission tomography and function by echocardiographic strain

Wed, 01 Feb 2023 00:00:00 +0000

Response to cardiac resynchronization therapy (CRT) is reduced in patients with high left ventricular (LV) scar burden, in particular when scar is located in the LV lateral wall or septum. Late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) can identity scar, but is not feasible in all patients. This study investigates if myocardial metabolism by ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) and contractile function by echocardiographic strain are alternatives to LGE-CMR. In a prospective multicenter study, 132 CRT candidates (91% with left bundle branch block) were studied by speckle tracking strain echocardiography, and 53 of these by FDG-PET. Regional myocardial FDG metabolism and peak systolic strain were compared to LGE-CMR as reference method. Reduced FDG metabolism (<70% relative) precisely identified transmural scars (≥50% of myocardial volume) in the LV lateral wall, with area under the curve (AUC) 0.96 (95% confidence interval (CI) 0.90-1.00). Reduced contractile function by strain identified transmural scars in the LV lateral wall with only moderate accuracy (AUC = 0.77, CI 0.71-0.84). However, absolute peak systolic strain >10% could rule out transmural scar with high sensitivity (80%) and high negative predictive value (96%). Neither FDG-PET nor strain identified septal scars (for both, AUC < 0.80). In CRT candidates, FDG-PET is an excellent alternative to LGE-CMR to identify scar in the LV lateral wall. Furthermore, preserved strain in the LV lateral wall has good accuracy to rule out transmural scar. None of the modalities can identify septal scar. The present study is part of the clinical study "Contractile Reserve in Dyssynchrony: A Novel Principle to Identify Candidates for Cardiac Resynchronization Therapy (CRID-CRT)", which was registered at clinicaltrials.gov (identifier NCT02525185).

Imaging the tumour microenvironment in rectal cancer: Decline in tumour blood flow during radiotherapy predicts good outcome

Mon, 23 Jan 2023 00:00:00 +0000

Measuring rectal tumour response to radiation is pivotal to restaging patients and for possibly stratification to a watch-and-wait strategy. Recognizing the importance of the tumour microenvironment, we investigated a less explored quantitative imaging marker assessing tumour blood flow (BF) for its potential to predict overall survival (OS). 24 rectal cancer patients given curative-intent neoadjuvant radiotherapy underwent a multi-echo dynamic magnetic resonance imaging (MRI) sequence with gadolinium contrast for quantification of tumour BF before either 25x2 Gy (n = 18) with concomitant chemotherapy or 5x5 Gy (n = 6). CD34 staining of excised tumour tissue was performed and baseline blood samples were analysed for lactate dehydrogenase (LDH) and angiopoietin-2 (ANGPT-2). Tumour volumes were measured before and after treatment. After subsequent surgery, ypTN scoring assessed tumour response. Cox regression for 5-year OS analysis and t-test for group comparisons were performed. The change in tumour BF (ΔBF) during neoadjuvant radiotherapy was a significant marker of OS, whereas tumour stage and volume were not related to OS. All patients with >20 % decline in BF were long-term survivors. Separating cases in two groups based on ΔBF revealed that patients with increase or a low decrease had higher baseline LDH (p = 0.032) and ANGPT-2 (p = 0.028) levels. MRI-assessed tumour ΔBF during neoadjuvant treatment is a significant predictor of OS in rectal cancer patients, making ΔBF a potential quantitative imaging biomarker for treatment stratification. Blood LDH and ANGPT-2 indicate that non-responding tumours may have a hypoxic microenvironment resistant to radiotherapy.

Risk of recurrence after chemoradiotherapy identified by multimodal MRI and 18F-FDG-PET/CT in locally advanced cervical cancer

Tue, 01 Nov 2022 00:00:00 +0000

MRI, applying dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) sequences, and 18F-fluorodeoxyglucose (18F-FDG) PET/CT provide information about tumor aggressiveness that is unexploited in treatment of locally advanced cervical cancer (LACC). We investigated the potential of a multimodal combination of imaging parameters for classifying patients according to their risk of recurrence. Eighty-two LACC patients with diagnostic MRI and FDG-PET/CT, treated with chemoradiotherapy, were collected. Thirty-eight patients with MRI only were included for validation of MRI results. Endpoints were survival (disease-free, cancer-specific, overall) and tumor control (local, locoregional, distant). K^trans, reflecting vascular function, apparent diffusion coefficient (ADC), reflecting cellularity, and standardized uptake value (SUV), reflecting glucose uptake, were extracted from DCE-MR, DW-MR and FDG-PET images, respectively. By applying an oxygen consumption and supply-based method, ADC and K^trans parametric maps were voxel-wise combined into hypoxia images that were used to determine hypoxic fraction (HF). HF showed a stronger association with outcome than the single modality parameters. This association was confirmed in the validation cohort. Low HF identified low-risk patients with 95% precision. Based on the 50th SUV-percentile (SUV₅₀), patients with high HF were divided into an intermediate- and high-risk group with high and low SUV₅₀, respectively. This defined a multimodality biomarker, HF/SUV₅₀. HF/SUV₅₀ increased the precision of detecting high-risk patients from 41% (HF alone) to 57% and showed prognostic significance in multivariable analysis for all endpoints. Multimodal combination of MR- and FDG-PET/CT-images improves classification of LACC patients compared to single modality images and clinical factors.

Correction to: Quantitative SPECT/CT imaging of lead-212: a phantom study

Mon, 10 Oct 2022 00:00:00 +0000

No abstract available

Comparison of [18F]fluciclovine and [18F]FDG PET/CT in Newly Diagnosed Multiple Myeloma Patients

Sat, 01 Oct 2022 00:00:00 +0000

[¹⁸F]FDG PET/CT in multiple myeloma (MM) is currently the best technology to demonstrate patchy and extramedullary disease. However, [¹⁸F]FDG PET has some limitations, and imaging with alternative tracers should be explored. In this study, we aimed to evaluate the performance of [¹⁸F]fluciclovine PET compared to [¹⁸F]FDG PET in newly diagnosed MM patients. Thirteen newly diagnosed transplant eligible MM patients were imaged both with [¹⁸F]FDG PET/CT and [¹⁸F]fluciclovine PET/CT within 1 week in a prospective study. The subjects were visually assessed positive or negative for disease. The number of lesions and the SUV_max of selected lesions were measured for both tracers. Furthermore, tracer uptake ratios were obtained by dividing lesion SUV_max by blood or bone marrow SUV_max. Between-group differences and correlations were assessed with paired t-tests and Pearson tests. Bone marrow SUVs were compared to bone marrow plasma cell percentage in biopsy samples. Nine subjects were assessed positively by [¹⁸F]FDG PET (69%) and 12 positives by [¹⁸F]fluciclovine PET (92%). All positive subjects had [¹⁸F]fluciclovine scans that were qualitatively scored as easier to interpret visually than the [¹⁸F]FDG scans. The number of lesions was also higher; seven of nine subjects with distinct hot spots on [¹⁸F]fluciclovine PET had fewer or no visible lesions on [¹⁸F]FDG PET. The mean lesion SUV_max values were 8.2 and 3.8 for [¹⁸F]fluciclovine and [¹⁸F]FDG, respectively. The mean tumour to blood values were 6.4 and 2.0 for [¹⁸F]fluciclovine and [¹⁸F]FDG, and the mean ratios between tumour and bone marrow were 2.1 and 1.5 for [¹⁸F]fluciclovine and [¹⁸F]FDG. The lesion SUV_max and ratios were significantly higher for [¹⁸F]fluciclovine (all p < 0.01). Local [¹⁸F]fluciclovine SUV_max or SUV_mean values in os ilium and the percentage of plasma cells in bone marrow biopsies were linearly correlated (p = 0.048). There were no significant correlations between [¹⁸F]FDG SUVs and plasma cells (p = 0.82). Based on this pilot study, [¹⁸F]fluciclovine is a promising tracer for MM. The visual and semi-quantitative evaluations indicate that [¹⁸F]fluciclovine PET/CT can out-perform [¹⁸F]FDG PET/CT at diagnosis.

FDG PET/CT and Dosimetric Studies of 177Lu-Lilotomab Satetraxetan in a First-in-Human Trial for Relapsed Indolent non-Hodgkin Lymphoma-Are We Hitting the Target?

Sat, 01 Oct 2022 00:00:00 +0000

[¹⁷⁷Lu]Lu-lilotomab satetraxetan, a novel CD37 directed radioimmunotherapy (RIT), has been investigated in a first-in-human phase 1/2a study for relapsed indolent non-Hodgkin lymphoma. In this study, new methods were assessed to calculate the mean absorbed dose to the total tumor volume, with the aim of establishing potential dose-response relationships based on 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET) parameters and clinical response. Our second aim was to study if higher total tumor burden induces reduction in the ¹⁷⁷Lu-lilotomab satetraxetan accumulation in tumor. Fifteen patients with different pre-dosing (non-radioactive lilotomab) regimens were included and the cohort was divided into low and high non-radioactive lilotomab pre-dosing groups for some of the analyses. ¹⁷⁷Lu-lilotomab satetraxetan was administered at dosage levels of 10, 15, or 20 MBq/kg. Mean absorbed doses to the total tumor volume (tTAD) were calculated from posttreatment single-photon emission tomography (SPECT)/computed tomography (CT) acquisitions. Total values of metabolic tumor volume (tMTV), total lesion glycolysis (tTLG) and the percent change in these parameters were calculated from FDG PET/CT performed at baseline, and at 3 and 6 months after RIT. Clinical responses were evaluated at 6 months as complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD). Significant decreases in tMTV and tTLG were observed at 3 months for patients receiving tTAD ≥ 200 cGy compared to patients receiving tTAD < 200 cGy (p = .03 for both). All non-responders had tTAD < 200 cGy. Large variations in tTAD were observed in responders. Reduction in ¹⁷⁷Lu-lilotomab satetraxetan uptake in tumor volume was not observed in patients with higher baseline tumor burden (tTMV). tTAD of ≥ 200 cGy may prove valuable to ensure clinical response, but further studies are needed to confirm this in a larger patient population. Furthermore, this work indicates that higher baseline tumor burden (up to 585 cm³) did not induce reduction in radioimmunoconjugate accumulation in tumor.

Radionuclides for Targeted Therapy: Physical Properties

Thu, 25 Aug 2022 00:00:00 +0000

A search in PubMed revealed that 72 radionuclides have been considered for molecular or functional targeted radionuclide therapy. As radionuclide therapies increase in number and variations, it is important to understand the role of the radionuclide and the various characteristics that can render it either useful or useless. This review focuses on the physical characteristics of radionuclides that are relevant for radionuclide therapy, such as linear energy transfer, relative biological effectiveness, range, half-life, imaging properties, and radiation protection considerations. All these properties vary considerably between radionuclides and can be optimised for specific targets. Properties that are advantageous for some applications can sometimes be drawbacks for others; for instance, radionuclides that enable easy imaging can introduce more radiation protection concerns than others. Similarly, a long radiation range is beneficial in targets with heterogeneous uptake, but it also increases the radiation dose to tissues surrounding the target, and, hence, a shorter range is likely more beneficial with homogeneous uptake. While one cannot select a collection of characteristics as each radionuclide comes with an unchangeable set, all the 72 radionuclides investigated for therapy-and many more that have not yet been investigated-provide numerous sets to choose between.

Quantitative SPECT/CT imaging of lead-212: a phantom study

Thu, 04 Aug 2022 00:00:00 +0000

Lead-212 (²¹²Pb) is a promising radionuclide for targeted therapy, as it decays to α-particle emitter bismuth-212 (²¹²Bi) via β-particle emission. This extends the problematic short half-life of ²¹²Bi. In preparation for upcoming clinical trials with ²¹²Pb, the feasibility of quantitative single photon-emission computed tomography/computed tomography (SPECT/CT) imaging of ²¹²Pb was studied, with the purpose to explore the possibility of individualised patient dosimetric estimation. Both acquisition parameters (combining two different energy windows and two different collimators) and iterative reconstruction parameters (varying the iterations x subsets between 10 × 1, 15 × 1, 30 × 1, 30 × 2, 30 × 3, 30 × 4, and 30 × 30) were investigated to evaluate visual quality and quantitative uncertainties based on phantom images. Calibration factors were determined using a homogeneous phantom and were stable when the total activity imaged exceeded 1 MBq for all the imaging protocols studied, but they increased sharply as the activity decayed below 1 MBq. Both a 20% window centred on 239 keV and a 40% window on 79 keV, with dual scatter windows of 5% and 20%, respectively, could be used. Visual quality at the lowest activity concentrations was improved with the High Energy collimator and the 79 keV energy window. Fractional uncertainty in the activity quantitation, including uncertainties from calibration factors and small volume effects, in spheres of 2.6 ml in the NEMA phantom was 16-21% for all protocols with the 30 × 4 filtered reconstruction except the High Energy collimator with the 239 keV energy window. Quantitative analysis was possible both with and without filters, but the visual quality of the images improved with a filter. Only minor differences were observed between the imaging protocols which were all determined suitable for quantitative imaging of ²¹²Pb. As uncertainties generally decreased with increasing iterative updates in the reconstruction and recovery curves did not converge with few iterations, a high number of reconstruction updates are recommended for quantitative imaging.

Mucosa-sparing dose painting of head and neck cancer

Tue, 01 Feb 2022 00:00:00 +0000

No abstract available

Deep learning-based automatic delineation of anal cancer gross tumour volume: a multimodality comparison of CT, PET and MRI

Sat, 01 Jan 2022 00:00:00 +0000

Accurate target volume delineation is a prerequisite for high-precision radiotherapy. However, manual delineation is resource-demanding and prone to interobserver variation. An automatic delineation approach could potentially save time and increase delineation consistency. In this study, the applicability of deep learning for fully automatic delineation of the gross tumour volume (GTV) in patients with anal squamous cell carcinoma (ASCC) was evaluated for the first time. An extensive comparison of the effects single modality and multimodality combinations of computed tomography (CT), positron emission tomography (PET), and magnetic resonance imaging (MRI) have on automatic delineation quality was conducted. 18F-fluorodeoxyglucose PET/CT and contrast-enhanced CT (ceCT) images were collected for 86 patients with ASCC. A subset of 36 patients also underwent a study-specific 3T MRI examination including T2- and diffusion-weighted imaging. The resulting two datasets were analysed separately. A two-dimensional U-Net convolutional neural network (CNN) was trained to delineate the GTV in axial image slices based on single or multimodality image input. Manual GTV delineations constituted the ground truth for CNN model training and evaluation. Models were evaluated using the Dice similarity coefficient (Dice) and surface distance metrics computed from five-fold cross-validation. CNN-generated automatic delineations demonstrated good agreement with the ground truth, resulting in mean Dice scores of 0.65-0.76 and 0.74-0.83 for the 86 and 36-patient datasets, respectively. For both datasets, the highest mean Dice scores were obtained using a multimodal combination of PET and ceCT (0.76-0.83). However, models based on single modality ceCT performed comparably well (0.74-0.81). T2W-only models performed acceptably but were somewhat inferior to the PET/ceCT and ceCT-based models. CNNs provided high-quality automatic GTV delineations for both single and multimodality image input, indicating that deep learning may prove a versatile tool for target volume delineation in future patients with ASCC.

Evaluation of semi-quantitative measures of 18F-flutemetamol PET for the clinical diagnosis of Alzheimer's disease

Sat, 01 Jan 2022 00:00:00 +0000

¹⁸F-flutemetamol positron emission tomography (PET) is used to assess cortical amyloid-β burden in patients with cognitive impairment to support a clinical diagnosis. Visual classification is the most widely used method in clinical practice although semi-quantification is beneficial to obtain an objective and continuous measure of the Aβ burden. The aims were: first to evaluate the correspondence between standardized uptake value ratios (SUVRs) from three different software, Centiloids and visual classification, second to estimate thresholds for supporting visual classification and last to assess differences in semi-quantitative measures between clinical diagnoses. This observational study included 195 patients with cognitive impairment who underwent ¹⁸F-flutemetamol PET. PET images were semi-quantified with SyngoVia, CortexID suite, and PMOD. Receiver operating characteristics curves were used to compare visual classification with composite SUVR normalized to pons (SUVRpons) and cerebellar cortex (SUVRcer), and Centiloids. We explored correlations and differences between semi-quantitative measures as well as differences in SUVR between two clinical diagnosis groups: Alzheimer’s disease-group and non-Alzheimer’s disease-group. PET images from 191 patients were semi-quantified with SyngoVia and CortexID and 86 PET-magnetic resonance imaging pairs with PMOD. All receiver operating characteristics curves showed a high area under the curve (>0.98). Thresholds for a visually positive PET was for SUVRcer: 1.87 (SyngoVia) and 1.64 (CortexID) and for SUVRpons: 0.54 (SyngoVia) and 0.55 (CortexID). The threshold on the Centiloid scale was 39.6 Centiloids. All semi-quantitative measures showed a very high correlation between different software and normalization methods. Composite SUVRcer was significantly different between SyngoVia and PMOD, SyngoVia and CortexID but not between PMOD and CortexID. Composite SUVRpons were significantly different between all three software. There were significant differences in the mean rank of SUVRpons, SUVRcer, and Centiloid between Alzheimer’s disease-group and non-Alzheimer’s disease-group. SUVR from different software performed equally well in discriminating visually positive and negative ¹⁸F-Flutemetamol PET images. Thresholds should be considered software-specific and cautiously be applied across software without preceding validation to categorize scans as positive or negative. SUVR and Centiloid may be used alongside a thorough clinical evaluation to support a clinical diagnosis.

Is Amyloid Burden Measured by 18F-Flutemetamol PET Associated with Progression in Clinical Alzheimer's Disease?

Sat, 01 Jan 2022 00:00:00 +0000

Patients with Alzheimer’s disease (AD) show heterogeneity in clinical progression rate, and we have limited tools to predict prognosis. Amyloid burden from 18F-Flutemetamol positron emission tomography (PET), as measured by standardized uptake value ratios (SUVR), might provide prognostic information. We investigate whether 18F-Flutemetamol PET composite or regional SUVRs are associated with trajectories of clinical progression. This observational longitudinal study included 94 patients with clinical AD. PET images were semi-quantified with normalization to pons. Group-based trajectory modeling was applied to identify trajectory groups according to change in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) over time. Multinomial logistic regression models assessed the association of SUVRs with trajectory group membership. Three trajectory groups were identified. In the regression models, neither composite nor regional SUVRs were associated with trajectory group membership. There were no associations between CDR progression and 18F-Flutemetamol PET-derived composite SUVRs or regional SUVRs in clinical AD.

EANM dosimetry committee series on standard operational procedures: a unified methodology for 99mTc-MAA pre- and 90Y peri-therapy dosimetry in liver radioembolization with 90Y microspheres

Fri, 12 Nov 2021 00:00:00 +0000

The aim of this standard operational procedure is to standardize the methodology employed for the evaluation of pre- and post-treatment absorbed dose calculations in ⁹⁰Y microsphere liver radioembolization. Basic assumptions include the permanent trapping of microspheres, the local energy deposition method for voxel dosimetry, and the patient-relative calibration method for activity quantification.The identity of ^99mTc albumin macro-aggregates (MAA) and ⁹⁰Y microsphere biodistribution is also assumed. The large observed discrepancies in some patients between ^99mTc-MAA predictions and actual ⁹⁰Y microsphere distributions for lesions is discussed. Absorbed dose predictions to whole non-tumoural liver are considered more reliable and the basic predictors of toxicity. Treatment planning based on mean absorbed dose delivered to the whole non-tumoural liver is advised, except in super-selective treatments.Given the potential mismatch between MAA simulation and actual therapy, absorbed doses should be calculated both pre- and post-therapy. Distinct evaluation between target tumours and non-tumoural tissue, including lungs in cases of lung shunt, are vital for proper optimization of therapy. Dosimetry should be performed first according to a mean absorbed dose approach, with an optional, but important, voxel level evaluation. Fully corrected ^99mTc-MAA Single Photon Emission Computed Tomography (SPECT)/computed tomography (CT) and ⁹⁰Y TOF PET/CT are regarded as optimal acquisition methodologies, but, for institutes where SPECT/CT is not available, non-attenuation corrected ^99mTc-MAA SPECT may be used. This offers better planning quality than non dosimetric methods such as Body Surface Area (BSA) or mono-compartmental dosimetry. Quantitative ⁹⁰Y bremsstrahlung SPECT can be used if dedicated correction methods are available.The proposed methodology is feasible with standard camera software and a spreadsheet. Available commercial or free software can help facilitate the process and improve calculation time.

Myelosuppression in patients treated with 177Lutetium-lilotomab satetraxetan can be predicted with absorbed dose to the red marrow as the only variable

Mon, 01 Nov 2021 00:00:00 +0000

The aim of this study was to investigate dosimetry data and clinical variables to predict hematological toxicity in non-Hodgkin lymphoma (NHL) patients treated with [¹⁷⁷Lutetium]Lu-lilotomab satetraxetan. A total of 17 patients treated with [¹⁷⁷Lu]Lu-lilotomab satetraxetan in a first-in-human phase 1/2a study were included. Absorbed dose to the red marrow was explored using SPECT/CT-imaging of the lumbar vertebrae L2-L4 over multiple time points. Percentage reduction of thrombocytes and neutrophils at nadir compared to baseline (PBN) and time to nadir (TTN) were chosen as indicators of myelosuppression and included as dependent variables. Two models were applied in the analysis, a multivariate linear model and a sigmoidal description of toxicity as a function of absorbed dose. A total of 10 independent patient variables were investigated in the multivariate analysis. Absorbed dose to the red marrow ranged from 1 to 4 Gy. Absorbed dose to the red marrow was found to be the only significant variable for PBN for both thrombocytes and neutrophils. The sigmoid function gave similar results in terms of accuracy when compared to the linear model. Myelosuppression in the form of thrombocytopenia and neutropenia in patients treated with [¹⁷⁷Lu]Lu-lilotomab satetraxetan can be predicted from the SPECT/CT-derived absorbed dose estimate to the red marrow.

A Pilot Study of a Parent Emotion Socialization Intervention: Impact on Parent Behavior, Child Self-Regulation, and Adjustment

Fri, 15 Oct 2021 00:00:00 +0000

Adequate emotion regulation in children is crucial for healthy development and is influenced by parent emotion socialization. The current pilot study aimed to test, for the first time in a Scandinavian population, whether an emotion-focused intervention, Tuning in to Kids (TIK), had positive effects on parent emotion-related socialization behaviors (ERSBs), and children’s self-regulation, anxiety, and externalizing behavior problems. We conducted a controlled trial of the 6-week evidence-based TIK parenting program with 20 parents of preschool children aged 5-6 years and 19 wait-list controls. Assessments at baseline and 6 months after the intervention included parent-report questionnaires on parent ERSBs and child adjustment, as well as aspects of children’s self-regulation assessed with two behavioral tasks, the Emotional Go/No-Go task (EGNG) and the AX-Continuous Performance Task (AX-CPT). Results showed a significant increase in reported parent emotion coaching behavior and an uncorrected significant decrease in parents’ report of child externalizing problems in intervention participants compared to controls. The behavioral data showed an uncorrected significant improvement in child emotion discrimination in the control condition compared to the intervention condition, while measures of children’s executive control improved from baseline to follow-up for both conditions but were not significantly different between conditions. These findings suggest that this emotion-focused parenting intervention contributed to improvement in parents’ emotion coaching and their appraisal of child externalizing problems, while children’s self-regulation showed mainly normative developmental improvements. Further research with a larger sample will be the next step to determine if these pilot findings are seen in an adequately powered study.

Localization of primary prostate cancer: FACBC PET/CT compared with multiparametric MRI using histopathology as reference standard

Fri, 15 Oct 2021 00:00:00 +0000

FACBC (anti-1-amino-3-¹⁸F-fluorocyclobutane-1-carboxylic acid) is a FDA-approved PET-tracer in patients with suspected recurrent prostate cancer. In the diagnostic work-up of primary prostate cancer, accurate localization of the index tumor is needed for image-guidance of biopsies. We therefore assessed the performance of FACBC PET/CT to detect and localize the index tumor and compared it to multiparametric MRI (mpMRI) using whole-mount histopathology as reference standard. Twenty-three patients with biopsy-proven prostate cancer had FACBC PET/CT and mpMRI within two weeks prior to prostatectomy. FACBC PET/CT was acquired as 14 minutes list-mode and re-binned into seven 2-minutes intervals. Static FACBC was the acquired data from 4-6 minutes, whereas the dynamic FACBC included all seven intervals. Two radiologists and two nuclear medicine physicians independently interpreted the images and consensus was reached in case of discrepancy. Static PET detected 15 of 23 (65%) of the index tumors, dynamic PET detected 14 of 22 (64%), and MRI detected 20 of 23 (87%). To assess the extent of the tumor, the interpreters delineated the tumor in a 12-regions sector-based template. True positive, true negative, false positive and false negative sectors were recorded based on the template drawings and whole-mount histopathology. Both static and dynamic FACBC PET had sensitivity of 40% and specificity of 99%, whereas MRI had sensitivity of 81% and specificity of 100%. Our data indicate that FACBC PET/CT may be useful but that mpMRI is better for localizing the index tumor in patients with prostate cancer.

Pembrolizumab in advanced osteosarcoma: results of a single-arm, open-label, phase 2 trial

Wed, 01 Sep 2021 00:00:00 +0000

To evaluate the activity and safety of the PD-1 antibody pembrolizumab in adult patients with advanced osteosarcoma. The study was a single-arm, open-label, phase 2 trial in patients with unresectable, relapsed osteosarcoma. The primary endpoint was clinical benefit rate (CBR) at 18 weeks of treatment, defined as complete response, partial response, or stable disease using RECIST v1.1. The trial had a Simon´s two-stage design, and ≥ 3 of 12 patients with clinical benefit in stage 1 were required to proceed to stage 2. The trial is registered with ClinicalTrials.gov, number NCT03013127. NanoString analysis was performed to explore tumor gene expression signatures and pathways. Twelve patients were enrolled and received study treatment. No patients had clinical benefit at 18 weeks of treatment, and patient enrollment was stopped after completion of stage 1. Estimated median progression-free survival was 1.7 months (95% CI 1.2-2.2). At time of data cut-off, 11 patients were deceased due to osteosarcoma. Median overall survival was 6.6 months (95% CI 3.8-9.3). No treatment-related deaths or drug-related grade 3 or 4 adverse events were observed. PD-L1 expression was positive in one of 11 evaluable tumor samples, and the positive sample was from a patient with a mixed treatment response. In this phase 2 study in advanced osteosarcoma, pembrolizumab was well-tolerated but did not show clinically significant antitumor activity. Future trials with immunomodulatory agents in osteosarcoma should explore combination strategies in patients selected based on molecular profiles associated with response.

Robotic salvage pelvic lymph node dissection for locoregional recurrence after radical prostatectomy: a single institution experience

Sun, 01 Aug 2021 00:00:00 +0000

To assess treatment response (PSA < 0.2 ng/ml), need for additional therapy and complication rate after robot assisted salvage pelvic lymph node dissection (sPLND). Analysis of outcomes data from radical prostatectomy (RP) patients consecutively operated with robot assisted sPLND due to biochemical recurrence and positron-emission tomography (PET)/computed tomography (CT)-detected nodal recurrence of pelvic lymph nodes. Sixty-nine patients underwent robotic sPLND after a median time of 47 months post- RP. Sixty-four patients (93%) had malignant lymph nodes upon histological assessment of sPLND specimen. Twenty patients (29%) achieved PSA < 0.2 ng/ml 6 weeks postoperatively. After median (IQR) follow-up of 15 months (10-27), fourteen patients (20%) still had PSA < 0.2 ng/ml without additional therapy and forty-one patients (59%) had started additional therapy. No significant predictor for treatment response was found. Postoperative complications occurred in 14 patients (20%). Eleven of these complications were classified as Clavien-Dindo grade 1. Oncological benefit of sPLND as the only salvage procedure seems to be limited, though almost one third of patients achieved treatment response. Clinical trials are needed to determine if sPLND as part of a multimodal treatment may improve outcome.

Left ventricular regional glucose metabolism in combination with septal scar extent identifies CRT responders

Thu, 01 Jul 2021 00:00:00 +0000

Cardiac resynchronization therapy (CRT) is effective in selective heart failure (HF) patients, but non-response rate remains high. Positron emission tomography (PET) may provide a better insight into the pathophysiology of left ventricular (LV) remodeling; however, its role for evaluating and selecting patients for CRT remains uncertain. We investigated if regional LV glucose metabolism in combination with myocardial scar could predict response to CRT. Consecutive CRT-eligible HF patients underwent echocardiography, cardiac magnetic resonance (CMR), and ¹⁸F-fluorodeoxyglucose (FDG) PET within 1 week before CRT implantation. Echocardiography was additionally performed 12 months after CRT and end-systolic volume reduction ≥ 15% was defined as CRT response. Septal-to-lateral wall (SLR) FDG uptake ratio was calculated from static FDG images. Late gadolinium enhancement (LGE) CMR was analyzed semi-quantitatively to define scar extent. We evaluated 88 patients (67 ± 10 years, 72% males). ¹⁸F-FDG SLR showed a linear correlation with volumetric reverse remodeling 12 months after CRT (r = 0.41, p = 0.0001). In non-ischemic HF patients, low FDG SLR alone predicted CRT response with sensitivity and specificity of more than 80%; however, in ischemic HF patients, specificity decreased to 46%, suggesting that in this cohort low SLR can also be caused by the presence of a septal scar. In the multivariate logistic regression model, including low FDG SLR, presence and extent of the scar in each myocardial wall, and current CRT guideline parameters, only low FDG SLR and septal scar remained associated with CRT response. Their combination could predict CRT response with sensitivity, specificity, negative, and positive predictive value of 80%, 83%, 70%, and 90%, respectively. FDG SLR can be used as a predictor of CRT response and combined with septal scar extent, CRT responders can be distinguished from non-responders with high diagnostic accuracy. Further studies are needed to verify whether this imaging approach can prospectively be used to optimize patient selection.

FDG PET/CT parameters and correlations with tumor-absorbed doses in a phase 1 trial of 177Lu-lilotomab satetraxetan for treatment of relapsed non-Hodgkin lymphoma

Tue, 01 Jun 2021 00:00:00 +0000

¹⁷⁷Lu-lilotomab satetraxetan targets the CD37 antigen and has been investigated in a first-in-human phase 1/2a study for relapsed non-Hodgkin lymphoma (NHL). Tumor dosimetry and response evaluation can be challenging after radioimmunotherapy (RIT). Changes in FDG PET/CT parameters after RIT and correlations with tumor-absorbed doses has not been examined previously in patients with lymphoma. Treatment-induced changes were measured at FDG PET/CT and ceCT to evaluate response at the lesion level after treatment, and correlations with tumor-absorbed doses were investigated. Forty-five tumors in 16 patients, with different pre-treatment and pre-dosing regimens, were included. Dosimetry was performed based on multiple SPECT/CT images. FDG PET/CT was performed at baseline and at 3 and 6 months. SUV_max, MTV, TLG, and changes in these parameters were calculated for each tumor. Lesion response was evaluated at 3 and 6 months (PET_3months and PET_6months) based on Deauville criteria. Anatomical changes based on ceCT at baseline and at 6 and 12 months were investigated by the sum of perpendiculars (SPD). Tumor-absorbed doses ranged from 35 to 859 cGy. Intra- and interpatient variations were observed. Mean decreases in PET parameters from baseline to 3 months were ΔSUV_max-3months 61%, ΔMTV_3months 80%, and ΔTLG_3months 77%. There was no overall correlation between tumor-absorbed dose and change in FDG PET or ceCT parameters at the lesion level or significant difference in tumor-absorbed doses between metabolic responders and non-responders after treatment. Our analysis does not show any correlation between tumor-absorbed doses and changes in FDG PET or ceCT parameters for the included lesions. The combination regimen, including cold antibodies, may be one of the factors precluding such a correlation. Increased intra-patient response with increased tumor-absorbed doses was observed for most patients, implying individual variations in radiation sensitivity or biology. ClinicalTrials.gov Identifier (NCT01796171). Registered December 2012.

18F-Fluciclovine PET for Assessment of Prostate Cancer with Histopathology as Reference Standard: A Systematic Review

Thu, 01 Apr 2021 00:00:00 +0000

The PET tracer ¹⁸F-fluciclovine (Axumin) was recently approved in the United States and Europe for men with suspected prostate cancer recurrence following prior treatment. This article summarizes studies where systematic sector-based histopathology was used as reference standard to assess the diagnostic accuracy of the tracer ¹⁸F-fluciclovine PET in patients with prostate cancer.

Assessment of Waldeyer's ring in pediatric and adolescent Hodgkin lymphoma patients-Importance of multimodality imaging: Results from the EuroNet-PHL-C1 trial

Thu, 01 Apr 2021 00:00:00 +0000

In the EuroNet Pediatric Hodgkin Lymphoma (EuroNet-PHL) trials, decision on Waldeyer’s ring (WR) involvement is usually based on clinical assessment, that is, physical examination and/or nasopharyngoscopy. However, clinical assessment only evaluates mucosal surface and is prone to interobserver variability. Modern cross-sectional imaging technology may provide valuable information beyond mucosal surface, which may lead to a more accurate WR staging. The EuroNet-PHL-C1 trial recruited 2102 patients, of which 1752 underwent central review including reference reading of their cross-sectional imaging data. In 14 of 1752 patients, WR was considered involved according to clinical assessment. In these 14 patients, the WR was re-assessed by applying an imaging-based algorithm considering information from ¹⁸ F-fluorodeoxyglucose positron emission tomography, contrast-enhanced computed tomography, and/or magnetic resonance imaging. For verification purposes, the imaging-based algorithm was applied to 100 consecutive patients whose WR was inconspicuous on clinical assessment. The imaging-based algorithm confirmed WR involvement only in four of the 14 patients. Of the remaining 10 patients, four had retropharyngeal lymph node involvement and six an inconspicuous WR. Applying the imaging-based algorithm to 100 consecutive patients with physiological appearance of their WR on clinical assessment, absence of WR involvement could be confirmed in 99. However, suspicion of WR involvement was raised in one patient. The imaging-based algorithm was feasible and easily applicable at initial staging of young patients with Hodgkin lymphoma. It increased the accuracy of WR staging, which may contribute to a more individualized treatment in the future.

Prostate-Specific Membrane Antigen PET for Assessment of Primary and Recurrent Prostate Cancer with Histopathology as Reference Standard: A Systematic Review and Meta-Analysis

Thu, 01 Apr 2021 00:00:00 +0000

Prostate-specific membrane antigen PET is a promising diagnostic tool in prostate cancer. The gold standard for the detection of prostate tumor and lymph node metastases is histopathology. The aim of the present review was to investigate accuracy measures of ⁶⁸Ga/¹⁸F-labeled prostate-specific membrane antigen PET tracers in primary and recurrent prostate cancer with systematic sector-based histopathology as the reference standard. A systematic literature search was performed and 34 studies were included. Overall, prostate-specific membrane antigen PET showed high specificity, but variable sensitivity to localize known prostate cancer and detect pelvic lymph node metastases.

Granulomatous-Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency-Features of CT and 18F-FDG Positron Emission Tomography/CT in Clinically Progressive Disease

Tue, 26 Jan 2021 00:00:00 +0000

Common variable immunodeficiency (CVID) is characterized not only by recurrent bacterial infections, but also autoimmune and inflammatory complications including interstitial lung disease (ILD), referred to as granulomatous-lymphocytic interstitial lung disease (GLILD). Some patients with GLILD have waxing and waning radiologic findings, but preserved pulmonary function, while others progress to end-stage respiratory failure. We reviewed 32 patients with radiological features of GLILD from our Norwegian cohort of CVID patients, including four patients with possible monogenic defects. Nineteen had deteriorating lung function over time, and 13 had stable lung function, as determined by pulmonary function testing of forced vital capacity (FVC), and diffusion capacity of carbon monoxide (DLCO). The overall co-existence of other non-infectious complications was high in our cohort, but the prevalence of these was similar in the two groups. Laboratory findings such as immunoglobulin levels and T- and B-cell subpopulations were also similar in the progressive and stable GLILD patients. Thoracic computer tomography (CT) scans were systematically evaluated and scored for radiologic features of GLILD in all pulmonary segments. Pathologic features were seen in all pulmonary segments, with traction bronchiectasis as the most prominent finding. Patients with progressive disease had significantly higher overall score of pathologic features compared to patients with stable disease, most notably traction bronchiectasis and interlobular septal thickening. 18F-2-fluoro-2-deoxy-D-glucose (¹⁸F-FDG) positron emission tomography/CT (PET/CT) was performed in 17 (11 with progressive and six with stable clinical disease) of the 32 patients and analyzed by quantitative evaluation. Patients with progressive disease had significantly higher mean standardized uptake value (SUVmean), metabolic lung volume (MLV) and total lung glycolysis (TLG) as compared to patients with stable disease. Nine patients had received treatment with rituximab for GLILD. There was significant improvement in pathologic features on CT-scans after treatment while there was a variable effect on FVC and DLCO. Patients with progressive GLILD as defined by deteriorating pulmonary function had significantly greater pathology on pulmonary CT and FDG-PET CT scans as compared to patients with stable disease, with traction bronchiectasis and interlobular septal thickening as prominent features.

Phase 1/2a study of 177Lu-lilotomab satetraxetan in relapsed/refractory indolent non-Hodgkin lymphoma

Tue, 08 Sep 2020 00:00:00 +0000

For patients with indolent non-Hodgkin lymphoma who fail initial anti-CD20-based immunochemotherapy or develop relapsed or refractory disease, there remains a significant unmet clinical need for new therapeutic approaches to improve outcomes and quality of life. 177Lu-lilotomab satetraxetan is a next-generation single-dose CD37-directed radioimmunotherapy (RIT) which was investigated in a phase 1/2a study in 74 patients with relapsed/refractory indolent non-Hodgkin B-cell lymphoma, including 57 patients with follicular lymphoma (FL). To improve targeting of 177Lu-lilotomab satetraxetan to tumor tissue and decrease hematologic toxicity, its administration was preceded by the anti-CD20 monoclonal antibody rituximab and the "cold" anti-CD37 antibody lilotomab. The most common adverse events (AEs) were reversible grade 3/4 neutropenia (31.6%) and thrombocytopenia (26.3%) with neutrophil and platelet count nadirs 5 to 7 weeks after RIT. The most frequent nonhematologic AE was grade 1/2 nausea (15.8%). With a single administration, the overall response rate was 61% (65% in patients with FL), including 30% complete responses. For FL with ≥2 prior therapies (n = 37), the overall response rate was 70%, including 32% complete responses. For patients with rituximab-refractory FL ≥2 prior therapies (n = 21), the overall response rate was 67%, and the complete response rate was 24%. The overall median duration of response was 13.6 months (32.0 months for patients with a complete response). 177Lu-lilotomab satetraxetan may provide a valuable alternative treatment approach in relapsed/refractory non-Hodgkin lymphoma, particularly in patients with comorbidities unsuitable for more intensive approaches. This trial was registered at www.clinicaltrials.gov as #NCT01796171.

EANM Dosimetry Committee series on standard operational procedures for internal dosimetry for 131I mIBG treatment of neuroendocrine tumours

Fri, 06 Mar 2020 00:00:00 +0000

The purpose of the EANM Dosimetry Committee Series on "Standard Operational Procedures for Dosimetry" (SOP) is to provide advice to scientists and clinicians on how to perform patient-specific absorbed dose assessments. This SOP describes image and data acquisition parameters and dosimetry calculations to determine the absorbed doses delivered to whole-body, tumour and normal organs following a therapeutic administration of ¹³¹I mIBG for the treatment of neuroblastoma or adult neuroendocrine tumours. Recommendations are based on evidence in recent literature where available and on expert opinion within the community. This SOP is intended to promote standardisation of practice within the community and as such is based on the facilities and expertise that should be available to any centre able to perform specialised treatments with radiopharmaceuticals and patient-specific dosimetry. A clinical example is given to demonstrate the application of the absorbed dose calculations.

Regional myocardial work by cardiac magnetic resonance and non-invasive left ventricular pressure: a feasibility study in left bundle branch block

Sat, 01 Feb 2020 00:00:00 +0000

Regional myocardial work may be assessed by pressure-strain analysis using a non-invasive estimate of left ventricular pressure (LVP). Strain by speckle tracking echocardiography (STE) is not always accessible due to poor image quality. This study investigated the estimation of regional myocardial work from strain by feature tracking (FT) cardiac magnetic resonance (CMR) and non-invasive LVP. Thirty-seven heart failure patients with reduced ejection fraction, left bundle branch block (LBBB), and no myocardial scar were compared to nine controls without LBBB. Circumferential strain was measured by FT-CMR in a mid-ventricular short-axis cine view, and longitudinal strain by STE. Segmental work was calculated by pressure-strain analysis. Twenty-five patients underwent 18F-fluorodeoxyglucose (FDG) positron emission tomography. Segmental values were reported as percentages of the segment with maximum myocardial FDG uptake. In LBBB patients, net CMR-derived work was 51 ± 537 (mean ± standard deviation) in septum vs. 1978 ± 1084 mmHg·% in the left ventricular (LV) lateral wall (P < 0.001). In controls, however, there was homogeneous work distribution with similar values in septum and the LV lateral wall (non-significant). Reproducibility was good. Segmental CMR-derived work correlated with segmental STE-derived work and with segmental FDG uptake (average r = 0.71 and 0.80, respectively). FT-CMR in combination with non-invasive LVP demonstrated markedly reduced work in septum compared to the LV lateral wall in patients with LBBB. Work distribution correlated with STE-derived work and energy demand as reflected in FDG uptake. These results suggest that FT-CMR in combination with non-invasive LVP is a relevant clinical tool to measure regional myocardial work.

A Nordic survey of CT doses in hybrid PET/CT and SPECT/CT examinations

Mon, 16 Dec 2019 00:00:00 +0000

Computed tomography (CT) scans are routinely performed in positron emission tomography (PET) and single photon emission computed tomography (SPECT) examinations globally, yet few surveys have been conducted to gather national diagnostic reference level (NDRL) data for CT radiation doses in positron emission tomography/computed tomography (PET/CT) and single photon emission computed tomography/computed tomography (SPECT/CT). In this first Nordic-wide study of CT doses in hybrid imaging, Nordic NDRL CT doses are suggested for PET/CT and SPECT/CT examinations specific to the clinical purpose of CT, and the scope for optimisation is evaluated. Data on hybrid imaging CT exposures and clinical purpose of CT were gathered for 5 PET/CT and 8 SPECT/CT examinations via designed booklet. For each included dataset for a given facility and scanner type, the computed tomography dose index by volume (CTDI_vol) and dose length product (DLP) was interpolated for a 75-kg person (referred to as CTDI_vol,75kg and DLP_75kg). Suggested NDRL (75th percentile) and achievable doses (50th percentile) were determined for CTDI_vol,75kg and DLP_75kg according to clinical purpose of CT. Differences in maximum and minimum doses (derived for a 75-kg patient) between facilities were also calculated for each examination and clinical purpose. Data were processed from 83 scanners from 43 facilities. Data were sufficient to suggest Nordic NDRL CT doses for the following: PET/CT oncology (localisation/characterisation, 15 systems); infection/inflammation (localisation/characterisation, 13 systems); brain (attenuation correction (AC) only, 11 systems); cardiac PET/CT and SPECT/CT (AC only, 30 systems); SPECT/CT lung (localisation/characterisation, 12 systems); bone (localisation/characterisation, 30 systems); and parathyroid (localisation/characterisation, 13 systems). Great variations in dose were seen for all aforementioned examinations. Greatest differences in DLP_75kg for each examination, specific to clinical purpose, were as follows: SPECT/CT lung AC only (27.4); PET/CT and SPECT/CT cardiac AC only (19.6); infection/inflammation AC only (18.1); PET/CT brain localisation/characterisation (16.8); SPECT/CT bone localisation/characterisation (10.0); PET/CT oncology AC only (9.0); and SPECT/CT parathyroid localisation/characterisation (7.8). Suggested Nordic NDRL CT doses are presented according to clinical purpose of CT for PET/CT oncology, infection/inflammation, brain, PET/CT and SPECT/CT cardiac, and SPECT/CT lung, bone, and parathyroid. The large variation in doses suggests great scope for optimisation in all 8 examinations.

Re: Tumor Targeting and Three-Dimensional Voxel-Based Dosimetry to Predict Tumor Response, Toxicity, and Survival after Yttrium-90 Resin Microsphere Radioembolization in Hepatocellular Carcinoma

Sun, 01 Dec 2019 00:00:00 +0000

No abstract available

Amyloid-β PET-Correlation with cerebrospinal fluid biomarkers and prediction of Alzheimer´s disease diagnosis in a memory clinic

Tue, 20 Aug 2019 00:00:00 +0000

Alzheimer’s disease (AD) remains a clinical diagnosis but biomarkers from cerebrospinal fluid (CSF) and more lately amyloid imaging with positron emission tomography (PET), are important to support a diagnosis of AD. To compare amyloid-β (Aβ) PET imaging with biomarkers in CSF and evaluate the prediction of Aβ PET on diagnosis in a memory clinic setting. We included 64 patients who had lumbar puncture and Aβ PET with 18F-Flutemetamol performed within 190 days. PET was binary classified (Flut+ or Flut-) and logistic regression analyses for correlation to each CSF biomarker; Aβ 42 (Aβ42), total tau (T-tau) and phosphorylated tau (P-tau), were performed. Cut-off values were assessed by receiver operating characteristic (ROC) curves. Logistic regression was performed for prediction of clinical AD diagnosis. We assessed the interrater agreement of PET classification as well as for diagnoses, which were made both with and without knowledge of PET results. Thirty-two of the 34 patients (94%) in the Flut+ group and nine of the 30 patients (30%) in the Flut- group had a clinical AD diagnosis. There were significant differences in all CSF biomarkers in the Flut+ and Flut- groups. Aβ42 showed the highest correlation with 18F-Flutemetamol PET with a cut-off value of 706.5 pg/mL, corresponding to sensitivity of 88% and specificity of 87%. 18F-Flutemetamol PET was the best predictor of a clinical AD diagnosis. We found a very high interrater agreement for both PET classification and diagnosis. The present study showed an excellent correlation of Aβ42 in CSF and 18F-Flutemetamol PET and the presented cut-off value for Aβ42 yields high sensitivity and specificity for 18F-Flutemetamol PET. 18F-Flutemetamol PET was the best predictor of clinical AD diagnosis.

Metastatic-directed therapy using PSMA-PET/CT at PSA relapse

Fri, 09 Aug 2019 00:00:00 +0000

The side effects of androgen deprivation therapy (ADT) as general treatment against prostate cancer are known to impair quality of life. However, the optimal onset of ADT at PSA relapse is unknown, especially in patients with normal testosterone. In our case a limited PSMA avid lymph node was detected on PET/CT. Our case highlights the importance of metastasis-directed therapy balancing general versus tailored treatment in the decision making in the era of advanced molecular imaging. By using PSMA-PET/CT and radiation we were able to pinpoint the metastasis prolonging the ADT-free survival, thus sparing the patient the side-effects of continuous ADT.

18F-Fluciclovine PET/CT in Suspected Residual or Recurrent High-Grade Glioma

Thu, 01 Aug 2019 00:00:00 +0000

To retrospectively investigate the uptake of F-fluciclovine on PET/CT in patients with suspected recurrent high-grade glioma (HGG). Twenty-one patients were included. The standard of truth was histopathologic interpretation if available. When histopathology was not available or rebiopsy did not show signs of malignancy, clinical follow-up including MRI and clinical outcome was considered the standard of truth. All 21 patients met the reference standard of either histopathologic proof of HGG recurrence (n = 10) or disease progression clinically and with tumor growth corresponding to the primary tumor sites on follow-up MRI (n = 11). Median time from PET/CT to death was 5 months (range, 1-20 months). Median time from primary diagnosis to death was 14.5 months (range, 6 to >400). Average SUVmax of the lesions was 8.3 ± 5.3 (SD) and 0.34 ± 0.13 for normal brain tissue. Median lesion-to-background ratio was 21.6 (range, 3.1-84.4). In 4 patients, F-fluciclovine PET/CT detected small satellite tumors that had not been reported on MR. The uptake of F-fluciclovine in clinically and/or histopathologically confirmed recurrent HGG is high compared with the uptake reported for other amino acid PET tracers. Because of the high tumor uptake and thus high tracer contrast, small satellite tumors with a diameter below usual reported PET spatial resolution and not reported on MRI were detected in 4 patients. As no patients with confirmed treatment-related changes were included, we cannot as of yet ascertain the ability of F-fluciclovine PET to discriminate between recurrent HGG and treatment-related changes, for example, pseudoprogression and radionecrosis.

Anal cancer chemoradiotherapy outcome prediction using 18F-fluorodeoxyglucose positron emission tomography and clinicopathological factors

Wed, 01 May 2019 00:00:00 +0000

To assess the role of [¹⁸F]fluorodeoxyglucose (FDG) positron emission tomography (PET), obtained before and during chemoradiotherapy, in predicting locoregional failure relative to clinicopathological factors for patients with anal cancer. 93 patients with anal squamous cell carcinoma treated with chemoradiotherapy were included in a prospective observational study (NCT01937780). FDG-PET/CT was performed for all patients before treatment, and for a subgroup (n = 39) also 2 weeks into treatment. FDG-PET was evaluated with standardized uptake values (SUV_{max/peak/mean}), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and a proposed Z-normalized combination of MTV and SUV_peak (ZMP). The objective was to predict locoregional failure using FDG-PET, tumor and lymph node stage, gross tumor volume (GTV) and human papilloma virus (HPV) status in univariate and bivariate Cox regression analysis. N3 lymph node stage, HPV negative tumor, GTV, MTV, TLG and ZMP were in univariate analysis significant predictors of locoregional failure (p < 0.01), while SUV_{max/peak/mean} were not (p > 0.2). In bivariate analysis HPV status was the most independent predictor in combinations with N3 stage, ZMP, TLG, and MTV (p < 0.02). The FDG-PET parameters at 2 weeks into radiotherapy decreased by 30-40 % of the initial values, but neither absolute nor relative decrease improved the prediction models. Pre-treatment PET parameters are predictive of chemoradiotherapy outcome in anal cancer, although HPV negativity and N3 stage are the strongest single predictors. Predictions can be improved by combining HPV with PET parameters such as MTV, TLG or ZMP. PET 2 weeks into treatment does not provide added predictive value. Pre-treatment PET parameters of anal cancer showed a predictive role independent of clinicopathological factors. Although the PET parameters show substantial reduction from pre- to mid-treatment, the changes were not predictive of chemoradiotherapy outcome.

Mapping Bone Marrow Response in the Vertebral Column by Positron Emission Tomography Following Radiotherapy and Erlotinib Therapy of Lung Cancer

Mon, 01 Apr 2019 00:00:00 +0000

To map functional bone marrow (BM) by 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) positron emission tomography (PET) in the vertebral column of lung cancer patients prior to, during, and after treatment. Moreover, to identify radiation- and erlotinib-induced changes in the BM. Twenty-six patients with advanced non-small cell lung cancer, receiving radiotherapy (RT) alone or concomitantly with erlotinib, were examined by [¹⁸F]FDG PET before, during, and after treatment. A total of 61 [¹⁸F]FDG PET scans were analyzed. Vertebral column BM [¹⁸F]FDG standardized uptake value normalized to the liver (SUV_BMLR) was used as uptake measure. Wilcoxon signed-rank test was used to assess changes in BM uptake of [¹⁸F]FDG between sessions. Effects of erlotinib on the BM activity during and after treatment were assessed using Mann-Whitney U test. A homogeneous uptake of [¹⁸F]FDG was observed within the vertebral column prior to treatment. Mean SUV_BMLR (± S.E.M) in the body of thoracic vertebrae receiving a total RT dose of 10 Gy or higher was 0.64 ± 0.01, 0.56 ± 0.01, and 0.59 ± 0.01 at pre-, mid-, and post-therapy, respectively. A significant reduction in the mean SUV_BMLR was observed from pre- to both mid- and post-therapy (p < 0.05). Mean SUV_BMLR was significantly higher at post-therapy compared to mid-therapy for patients receiving erlotinib in addition to RT (p < 0.05). RT reduces BM [¹⁸F]FDG uptake in the vertebral column, especially in the high-dose region. Concomitant erlotinib may stimulate a recovery in BM [¹⁸F]FDG uptake from mid- to post-therapy. NCT02714530. Registered 10 September 2015.

Ocular signatures of proactive versus reactive cognitive control in young adults

Mon, 01 Oct 2018 00:00:00 +0000

During the execution of a cognitive task, the brain maintains contextual information to guide behavior and achieve desired goals. The AX-Continuous Performance Task is used to study proactive versus reactive cognitive control. Young adults tend to behave proactively in standard testing conditions. However, it remains unclear how interindividual variability (e.g., in cognitive and motivational factors) may drive people into more reactive or proactive control under the same task demands. We investigated the use of control strategies in a large population of healthy young adults. We computed the proactive behavioral index and consequently divided participants into proactive, reactive, and intermediate groups. We found that reactive participants were generally slower, presented lower context sensitivity, and larger response variability. Pupillary changes and blink rate index cognitive effort allocation. We measured, concomitantly to the task, the pupil size and frequency of blinks associated with the cue maintenance and response intervals. During the cue period, nonfrequent, nontarget cues led to increased pupil dilation and number of blinks in all participants. During the response interval, we found more errors and increased pupil dilation to the probe when all participants had to overcome a response bias generated by the frequent cue. Only reactive participants showed larger response-related pupil when they had to overcome a response bias related to the frequent probe. Contrary to expectations, groups did not differ in ocular measures in the cue period. In conclusion, interindividual differences in cognitive control between healthy adults can be mapped onto different patterns of effort allocation indexed by the pupil.

Osteonecrosis of the Jaw in a Patient With Bone Metastatic Prostate Cancer After Long-term Bisphosphonate Treatment With Severe Deterioration Following Radium-223

Mon, 01 Oct 2018 00:00:00 +0000

No abstract available

Low dose-rate irradiation with [3H]-labelled valine to selectively target hypoxic cells in a human colorectal cancer xenograft model

Sat, 01 Sep 2018 00:00:00 +0000

Earlier in vitro studies show that irradiation with an ultra-low dose-rate of 15 mGy/h delivered with [³H]-valine leads to loss of clonogenicity in hypoxic T-47D cells. Here, the aim was to determine if [³H]-valine could be used to deliver low dose-rate irradiation in a colorectal cancer model. Clonogenicity was measured in cultured cancer cell line HT29 irradiated with 15 mGy/h combined with intermittent hypoxia. Mice with HT29 xenografts were irradiated by repeated injections of [³H]-valine intravenously. The activity in the tumor tissue was measured by scintillation counting and tumor growth, hypoxic fraction and tritium distribution within tumors were assessed by pimonidazole staining and autoradiography. Ultra-low dose-rate irradiation decreased clonogenicity in hypoxic colorectal cancer cells. In vivo, the tumor growth, hypoxic fraction and weight of the mice were similar between the treated and untreated group. Autoradiography showed no [³H]-valine uptake in hypoxic tumor regions in contrast to aerobic tissue. Continuous low-dose-rate irradiation was well tolerated by aerobic tissue. This indicates a potential use of low dose-rate irradiation to target hypoxic tumor cells in combination with high dose-rate irradiation to eradicate the well oxygenated tumor regions. However, [³H]-valine is not the appropriate method to deliver ultra-low dose-rate irradiation in vivo.

The Effect of New Formulas for Lean Body Mass on Lean-Body-Mass-Normalized SUV in Oncologic 18F-FDG PET/CT

Sat, 01 Sep 2018 00:00:00 +0000

Because of better precision and intercompatibility, the use of lean body mass (LBM) as a mass estimate in the calculation of SUV (SUL) has become more common in research and clinical studies today. Thus, the equations deciding this quantity must be those that best represent the actual body composition.

Methods: LBM was calculated for 44 patients examined with ¹⁸F-FDG PET/CT scans by means of the sex-specific predictive equations of James and Janmahasatians, and the results were validated using a CT-based method that makes use of the eyes-to-thighs CT component of the PET/CT aquisition and segments the voxels according to Hounsfield units. Intraclass correlation coefficients and Bland-Altman plots were used to assess agreement between the various methods.

Results: A mean difference of 6.3 kg (limits of agreement, -15.1 to 2.5 kg) between [Formula: see text] and [Formula: see text] was found. This difference was higher than the 3.8-kg difference observed between [Formula: see text] and [Formula: see text] (limits of agreement, -12.5 to 4.9 kg). In addition, [Formula: see text] had a higher intraclass correlation coefficient with [Formula: see text] (0.87; 95% confidence interval, 0.60-0.94) than with [Formula: see text] (0.77; 95% confidence interval, 0.11-0.91). Thus, we obtained better agreement between [Formula: see text] and [Formula: see text] Although there were exceptions, the overall effect on SUL was that [Formula: see text] was greater than [Formula: see text]

Conclusion: We have verified the reliability of the suggested [Formula: see text] formulas with a CT-derived reference standard. Compared with the more traditional and available set of [Formula: see text] equations, the [Formula: see text] formulas tend to yield better agreement.

Pre-dosing with lilotomab prior to therapy with 177Lu-lilotomab satetraxetan significantly increases the ratio of tumor to red marrow absorbed dose in non-Hodgkin lymphoma patients

Sun, 01 Jul 2018 00:00:00 +0000

¹⁷⁷Lu-lilotomab satetraxetan is a novel anti-CD37 antibody radionuclide conjugate for the treatment of non-Hodgkin lymphoma (NHL). Four arms with different combinations of pre-dosing and pre-treatment have been investigated in a first-in-human phase 1/2a study for relapsed CD37+ indolent NHL. The aim of this work was to determine the tumor and normal tissue absorbed doses for all four arms, and investigate possible variations in the ratios of tumor to organs-at-risk absorbed doses. Two of the phase 1 arms included cold lilotomab pre-dosing (arm 1 and 4; 40 mg fixed and 100 mg/m² BSA dosage, respectively) and two did not (arms 2 and 3). All patients were pre-treated with different regimens of rituximab. The patients received either 10, 15, or 20 MBq ¹⁷⁷Lu-lilotomab satetraxetan per kg body weight. Nineteen patients were included for dosimetry, and a total of 47 lesions were included. The absorbed doses were calculated from multiple SPECT/CT-images and normalized by administered activity for each patient. Two-sided Student’s t tests were used for all statistical analyses. Organs with distinct uptake of ¹⁷⁷Lu-lilotomab satetraxetan, in addition to tumors, were red marrow (RM), liver, spleen, and kidneys. The mean RM absorbed doses were 0.94, 1.55, 1.44, and 0.89 mGy/MBq for arms 1-4, respectively. For the patients not pre-dosed with lilotomab (arms 2 and 3 combined) the mean RM absorbed dose was 1.48 mGy/MBq, which was significantly higher than for both arm 1 (p = 0.04) and arm 4 (p = 0.02). Of the other organs, the highest uptake was found in the spleen, and there was a significantly lower spleen absorbed dose for arm-4 patients than for the patient group without lilotomab pre-dosing (1.13 vs. 3.20 mGy/MBq; p < 0.01). Mean tumor absorbed doses were 2.15, 2.31, 1.33, and 2.67 mGy/MBq for arms 1-4, respectively. After averaging the tumor absorbed dose for each patient, the patient mean tumor absorbed dose to RM absorbed dose ratios were obtained, given mean values of 1.07 for the patient group not pre-dosed with lilotomab, of 2.16 for arm 1, and of 4.62 for arm 4. The ratios were significantly higher in both arms 1 and 4 compared to the group without pre-dosing (p = 0.05 and p = 0.02). No statistically significant difference between arms 1 and 4 was found. RM is the primary dose-limiting organ for ¹⁷⁷Lu-lilotomab satetraxetan treatment, and pre-dosing with lilotomab has a mitigating effect on RM absorbed dose. Increasing the amount of lilotomab from 40 mg to 100 mg/m² was found to slightly decrease the RM absorbed dose and increase the ratio of tumor to RM absorbed dose. Still, both pre-dosing amounts resulted in significantly higher tumor to RM absorbed dose ratios. The findings encourage continued use of pre-dosing with lilotomab.

Biodistribution and Dosimetry Results from a Phase 1 Trial of Therapy with the Antibody-Radionuclide Conjugate 177Lu-Lilotomab Satetraxetan

Sun, 01 Apr 2018 00:00:00 +0000

¹⁷⁷Lu-lilotomab satetraxetan is a novel antibody-radionuclide conjugate currently in a phase 1/2a first-in-humans dose escalation trial for patients with relapsed CD37-positive indolent non-Hodgkin lymphoma. The aim of this study was to investigate biodistribution and absorbed doses to organs at risk.

Methods: In total, 7 patients treated with ¹⁷⁷Lu-lilotomab satetraxetan were included for dosimetry. Patients were grouped on the basis of 2 different predosing regimens (with and without predosing with 40 mg of lilotomab) and were treated with different levels of activity per body weight (10, 15, and 20 MBq/kg). All patients were pretreated with rituximab. Serial planar and SPECT/CT images were used to determine time-activity curves and patient-specific masses for organs with ¹⁷⁷Lu-lilotomab satetraxetan uptake. Doses were calculated with OLINDA/EXM.

Results: The organs (other than red bone marrow and tumors) with distinct uptake of ¹⁷⁷Lu-lilotomab satetraxetan were the liver, spleen, and kidneys. The highest uptake was found in the spleen, with doses ranging from 1.54 to 3.60 mGy/MBq. The liver received 0.70-1.15 mGy/MBq. The kidneys received the lowest dose of the source organs investigated, 0.16-0.79 mGy/MBq. No statistically significant differences in soft-tissue absorbed doses were found between the two predosing regimens. The whole-body dose ranged from 0.08 to 0.17 mGy/MBq.

Conclusion: The biodistribution study for patients treated with ¹⁷⁷Lu-lilotomab satetraxetan revealed the highest physiologic uptake to be in the liver and spleen (besides the red marrow). For all treatment levels investigated, the absorbed doses were found to be modest when compared with commonly assumed tolerance limits.

Serum cytokine profiles and metabolic tumor burden in patients with non-small cell lung cancer undergoing palliative thoracic radiation therapy

Tue, 13 Feb 2018 00:00:00 +0000

Radiation therapy effectively kills cancer cells and elicits local effects in the irradiated tissue. The aim of this study was to investigate the kinetics of cytokines in the serum of patients with lung cancer undergoing radiation therapy and to identify associations with metabolic tumor burden as determined by 2-deoxy-2-fluoro-D-glucose (¹⁸F-FDG) positron emission tomography (PET). Forty-five patients with advanced non-small cell lung cancer were included in a phase 2 clinical trial and randomized between fractionated thoracic radiation therapy alone or concurrent with an epidermal growth factor receptor inhibitor. Blood was sampled at 4 different time points: prior to treatment, midtherapy, at the end of therapy, and 6 to 8 weeks after the start of treatment. The serum concentrations of 48 cytokines and 9 matrix metalloproteinases were measured with multiplex immunoassays. A subset of patients was examined by ¹⁸F-FDG PET/computed tomography before, during, and after radiation therapy. The maximum standardized uptake values (SUV_max) of the primary lung tumor, whole-body metabolic tumor volume, and total lesion glycolysis were calculated, and correlations between the PET parameters and cytokines were investigated. The SUV_max decreased from baseline through midtherapy to posttherapy ¹⁸F-FDG PET/computed tomography (P = .018). The serum levels of C-C motif chemokine ligand (CCL) 23, CCL24, C-X3-C motif chemokine ligand 1, and interleukin-8 (C-X-C motif ligand [CXCL]8) were significantly correlated to SUV_max, metabolic tumor volume, and total lesion glycolysis before, during, and after radiation therapy. CXCL2 (P = .030) and CXCL6 (P = .010) decreased after the start of therapy and changed significantly across the sample time points. Serum concentrations of CCL15 (P = .031), CXCL2 (P = .028), and interleukin-6 (P = .007) were positively correlated to the irradiated volume during the second week of treatment. Cytokine serum levels vary and correlate with metabolic tumor burden in patients with advanced non-small cell lung cancer undergoing palliative thoracic radiation therapy.

Respiratory motion during 90Yttrium PET contributes to underestimation of tumor dose and overestimation of normal liver tissue dose

Thu, 01 Feb 2018 00:00:00 +0000

Background Yttrium-90 dosimetry after radioembolization is reliant on accurate quantitative imaging of the microsphere deposition. Previous studies have focused on the correction of geometrical resolution effects. Purpose To uncover additional effects of respiratory motion. Material and Methods Mathematical models describing spherical tumors were formed and two blurring effects, limited geometrical resolution and respiratory motion, were simulated. The virtual images were used as basis for dose volume histogram estimations by convolving the radioactivity representations with a dose point kernel. Results For respiratory motion only, the largest errors were found for the smallest tumors and/or tumors with heterogeneous distribution of yttrium-90 microspheres. The deviations in max dose and dose to 25% and 50% of the tumor volume were estimated at 20-40%, 10-30%, and 0-30%, respectively. Additional blurring from geometrical resolution increased the errors to 55-75%, 50-60%, and 25-60%, respectively. Conclusion Respiratory motion contributes to underestimation of tumor dose and overestimation of normal tissue dose.

Dosimetry-based treatment planning for molecular radiotherapy: a summary of the 2017 report from the Internal Dosimetry Task Force

Tue, 21 Nov 2017 00:00:00 +0000

The European directive on basic safety standards (Council directive 2013/59 Euratom) mandates dosimetry-based treatment planning for radiopharmaceutical therapies. The directive comes into operation February 2018, and the aim of a report produced by the Internal Dosimetry Task Force of the European Association of Nuclear Medicine is to address this aspect of the directive. A summary of the report is presented. A brief review of five of the most common therapy procedures is included in the current text, focused on the potential to perform patient-specific dosimetry. In the full report, 11 different therapeutic procedures are included, allowing additional considerations of effectiveness, references to specific literature on quantitative imaging and dosimetry, and existing evidence for absorbed dose-effect correlations for each treatment. Individualized treatment planning with tracer diagnostics and verification of the absorbed doses delivered following therapy is found to be scientifically feasible for almost all procedures investigated, using quantitative imaging and/or external monitoring. Translation of this directive into clinical practice will have significant implications for resource requirements. Molecular radiotherapy is undergoing a significant expansion, and the groundwork for dosimetry-based treatment planning is already in place. The mandated individualization is likely to improve the effectiveness of the treatments, although must be adequately resourced.

100 days with scans of the same Catphan phantom on the same CT scanner

Wed, 01 Nov 2017 00:00:00 +0000

Quality control (QC) of CT scanners is important to evaluate image quality and radiation dose. Different QC phantoms for testing image quality parameters on CT are commercially available, and Catphan phantoms are widely used for this purpose. More data from measured image quality parameters on CT are necessary to assess test methods, tolerance levels, and test frequencies. The aim of this study was to evaluate the stability of essential image quality parameters for axial and helical scans on one CT scanner over time. A Catphan 600 phantom was scanned on a Philips Ingenuity CT scanner for 100 days over a period of 6 months. At each day of testing, one helical scan covering the entire phantom and four axial scans covering four different modules in the phantom were performed. All images were uploaded into Image Owl for automatic analysis of CT numbers, modular transfer function (MTF), low-contrast resolution, noise, and uniformity. In general, the different image quality parameters for both scan techniques were stable over time compared to given tolerance levels. Average measured CT numbers differed between axial and helical scans, while MTF was almost identical for helical and axial scans. Axial scans had better low-contrast resolution and less noise than helical scans. The uniformity was relatively similar for axial and helical scans. Most standard deviations of measured values were larger for helical scans compared to axial scans. Test results in this study were stable over time for both scan techniques, but further studies on different CT scanners are required to confirm that this also holds true for other systems.

A new method to assess pulmonary changes using 18F-fluoro-2-deoxyglucose positron emission tomography for lung cancer patients following radiotherapy

Wed, 01 Nov 2017 00:00:00 +0000

¹⁸F-fluoro-2-deoxyglucose positron emission tomography (¹⁸F-FDG-PET) may be used for assessing radiation induced alterations in the lung. However, there is a need to further develop methodologies to improve quantification. Using computed tomography (CT), a local structure method has been shown to be superior to conventional CT-based analysis. Here, we investigate whether the local structure method based on ¹⁸F-FDG-PET improves radiotherapy (RT) dose-response quantification for lung cancer patients. Sixteen patients with lung cancer undergoing fractionated RT were examined by ¹⁸F-FDG-PET/CT at three sessions (pre, mid, post) and the lung was delineated in the planning CT images. The RT dose matrix was co-registered with the PET images. For each PET image series, mean (μ) and standard deviation (σ) maps were calculated based on cubes in the lung (3 × 3 × 3 voxels), where the spread in pre-therapy μ and σ was characterized by a covariance ellipse in a sub-volume of 3 × 3 × 3 cubes. Mahalanobis distance was used to measure the distance of individual cube values to the origin of the ellipse and to further form local structure ‘S’ maps. The structural difference maps (ΔS) and mean difference maps (Δμ) were calculated by subtracting pre-therapy maps from maps at mid- and post-therapy. Corresponding maps based on CT images were also generated. ΔS identified new areas of interest in the lung compared to conventional Δμ maps. ΔS for PET and CT gave a significantly elevated lung signal compared to a control group during and post-RT (p < .05). Dose-response analyses by linear regression showed that ΔS between pre- and post-therapy for ¹⁸F-FDG-PET was the only parameter significantly associated with local lung dose (p = .04). The new method using local structures on ¹⁸F-FDG-PET provides a clearer uptake dose-response compared to conventional analysis and CT-based approaches and may be valuable in future studies addressing lung toxicity.

Target volume delineation of anal cancer based on magnetic resonance imaging or positron emission tomography

Wed, 06 Sep 2017 00:00:00 +0000

To compare target volume delineation of anal cancer using positron emission tomography (PET) and magnetic resonance imaging (MRI) with respect to inter-observer and inter-modality variability. Nineteen patients with anal cancer undergoing chemoradiotherapy were prospectively included. Planning computed tomography (CT) images were co-registered with 18F-fluorodexocyglucose (FDG) PET/CT images and T2 and diffusion weighted (DW) MR images. Three oncologists delineated the Gross Tumor Volume (GTV) according to national guidelines and the visible tumor tissue (GTV_T). MRI and PET based delineations were evaluated by absolute volumes and Dice similarity coefficients. The median volume of the GTVs was 27 and 31 cm³ for PET and MRI, respectively, while it was 6 and 11 cm³ for GTV_T. Both GTV and GTV_T volumes were highly correlated between delineators (r = 0.90 and r = 0.96, respectively). The median Dice similarity coefficient was 0.75 when comparing the GTVs based on PET/CT (GTV_PET) with the GTVs based on MRI and CT (GTV_MRI). The median Dice coefficient was 0.56 when comparing the visible tumor volume evaluated by PET (GTV_{T_PET}) with the same volume evaluated by MRI (GTV_{T_MRI}). Margins of 1-2 mm in the axial plane and 7-8 mm in superoinferior direction were required for coverage of the individual observer’s GTVs. The rather good agreement between PET- and MRI-based GTVs indicates that either modality may be used for standard target delineation of anal cancer. However, larger deviations were found for GTV_T, which may impact future tumor boost strategies.

Temporal Processing in the Visual Cortex of the Awake and Anesthetized Rat

Mon, 07 Aug 2017 00:00:00 +0000

The activity pattern and temporal dynamics within and between neuron ensembles are essential features of information processing and believed to be profoundly affected by anesthesia. Much of our general understanding of sensory information processing, including computational models aimed at mathematically simulating sensory information processing, rely on parameters derived from recordings conducted on animals under anesthesia. Due to the high variety of neuronal subtypes in the brain, population-based estimates of the impact of anesthesia may conceal unit- or ensemble-specific effects of the transition between states. Using chronically implanted tetrodes into primary visual cortex (V1) of rats, we conducted extracellular recordings of single units and followed the same cell ensembles in the awake and anesthetized states. We found that the transition from wakefulness to anesthesia involves unpredictable changes in temporal response characteristics. The latency of single-unit responses to visual stimulation was delayed in anesthesia, with large individual variations between units. Pair-wise correlations between units increased under anesthesia, indicating more synchronized activity. Further, the units within an ensemble show reproducible temporal activity patterns in response to visual stimuli that is changed between states, suggesting state-dependent sequences of activity. The current dataset, with recordings from the same neural ensembles across states, is well suited for validating and testing computational network models. This can lead to testable predictions, bring a deeper understanding of the experimental findings and improve models of neural information processing. Here, we exemplify such a workflow using a Brunel network model.

Assessment of pulmonary 18F-FDG-PET uptake and cytokine profiles in non-small cell lung cancer patients treated with radiotherapy and erlotinib

Thu, 15 Jun 2017 00:00:00 +0000

To investigate effects of radiotherapy (RT) and erlotinib on pulmonary glucose uptake using 2-deoxy-2-(18F)fluoro-D-glucose (¹⁸F-FDG) positron emission tomography (PET) during and after treatment of non-small cell lung cancer (NSCLC) and to identify associations between serum cytokine levels and lung glucose uptake. Twenty-seven patients with advanced NSCLC, receiving RT alone or concomitant RT and erlotinib therapy, were examined by ¹⁸F-FDG PET before, during, and after treatment. A total of 57 ¹⁸F-FDG PET scans were analyzed. Pulmonary ¹⁸F-FDG uptake and radiotherapy dose mapping were used to acquire dose-response curves for each patient, where subsequent linear regression gave a glucose uptake level in the un-irradiated parts of the lungs (SUV₀) and a response slope (ΔSUV). Serum cytokine levels at corresponding time points were assessed using a multiplex bioassay. Correlations between the most robust cytokines and lung ¹⁸F-FDG dose response parameters were further investigated. From the dose response analysis, SUV₀ at post-therapy was significantly higher (P < 0.001) than at mid- and pre-therapy (45% and 58%, respectively) for the group receiving RT + erlotinib. Also, SUV₀ at post-therapy was higher for patients receiving RT + erlotinib compared to RT alone (42%; P < 0.001). No differences in ΔSUV were seen with treatments or time. SUV₀ was positively associated (r = 0.47, P = 0.01) with serum levels of the chemokine C-C motif ligand 21 (CCL21) for patients receiving RT + erlotinib. Concomitant RT and erlotinib causes an elevation in pulmonary ¹⁸F-FDG uptake post treatment compared to RT alone. Pulmonary glucose uptake is associated with an upregulation of a chemokine (CCL21) involved in inflammatory reactions.

Combining radioiodine and external beam radiation therapy: the potential of integrated treatment planning for differentiated thyroid cancer

Thu, 01 Jun 2017 00:00:00 +0000

No abstract available

Dynamic 2-Deoxy-2-[18F]Fluoro-D-Glucose Positron Emission Tomography for Chemotherapy Response Monitoring of Breast Cancer Xenografts

Sat, 01 Apr 2017 00:00:00 +0000

Non-invasive response monitoring can potentially be used to guide therapy selection for breast cancer patients. We employed dynamic 2-deoxy-2-[¹⁸F]fluoro-D-glucose positron emission tomography ([¹⁸F]FDG PET) to evaluate changes in three breast cancer xenograft lines in mice following three chemotherapy regimens. Sixty-six athymic nude mice bearing bilateral breast cancer xenografts (two basal-like and one luminal-like subtype) underwent three 60 min [¹⁸F]FDG PET scans. Scans were performed prior to and 3 and 10 days after treatment with doxorubicin, paclitaxel, or carboplatin. Tumor growth was monitored in parallel. A pharmacokinetic compartmental model was fitted to the tumor uptake curves, providing estimates of transfer rates between the vascular, non-metabolized, and metabolized compartments. Early and late standardized uptake values (SUV_E and SUV_L, respectively); the rate constants k ₁, k ₂, and k ₃, and the intravascular fraction v _B were estimated. Changes in tumor volume were used as a response measure. Multivariate partial least-squares regression (PLSR) was used to assess if PET parameters could model tumor response and to identify PET parameters with the largest impact on response. Treatment responders had significantly larger perfusion-related parameters (k ₁ and k ₂) and lower metabolism-related parameter (k ₃) than non-responders 10 days after the start of treatment. These findings were further supported by the PLSR analysis, which showed that k ₁ and k ₂ at day 10 and changes in k ₃ explained most of the variability in response to therapy, whereas SUV_L and particularly SUV_E were of lesser importance. Overall, rate parameters related to both tumor perfusion and metabolism were associated with tumor response. Conventional metrics of [¹⁸F]FDG uptake such as SUV_E and SUV_L apparently had little relation to tumor response, thus necessitating full dynamic scanning and pharmacokinetic analysis for optimal evaluation of chemotherapy-induced changes in breast cancers.

Denosumab in patients with giant-cell tumor of bone in Norway: results from a nationwide cohort

Wed, 01 Mar 2017 00:00:00 +0000

Denosumab is a relatively new treatment option for patients with giant-cell tumor of bone (GCTB). The purpose of this study was to report the results for patients treated in Norway. Patients treated with denosumab for GCTB were identified from the clinical databases at the Norwegian sarcoma reference centers. Data were retrieved from the clinical databases and supplemented by retrospective review of patient records. Denosumab was given as a subcutaneous injection every 4 weeks with loading doses on day 8 and 15 in cycle 1. Eighteen patients treated with denosumab for GCTB were identified. Denosumab was given for recurrent disease in seven cases and as first-line treatment in 11 patients, of which 6 received therapy as part of a neoadjuvant/adjuvant strategy and 5 for surgically unsalvageable primary tumor. Ten of 12 patients with unresectable disease are still on denosumab without progression with median treatment duration of 41 months (range 18-60). Two patients discontinued treatment due to osteonecrosis of the jaw and reduced compliance, respectively. In the adjuvant group, four patients experienced disease recurrence after stopping denosumab. In three of six patients, the extent of surgery was reduced due to neoadjuvant therapy. Seventeen of 18 patients underwent response evaluation with 18F-FDG PET/CT at median 4.7 weeks from starting denosumab. Median baseline SUV_max was 11.0 and median SUV_max at evaluation was 4.9 (p < 0.001). In a nationwide GCTB patient cohort, denosumab was an effective agent and durable responses were observed. Our results do not support the use of adjuvant therapy in routine clinical practice. 18F-FDG PET/CT could be a valuable tool for early response evaluation.

Red Marrow-Absorbed Dose for Non-Hodgkin Lymphoma Patients Treated with 177Lu-Lilotomab Satetraxetan, a Novel Anti-CD37 Antibody-Radionuclide Conjugate

Sun, 01 Jan 2017 00:00:00 +0000

Red marrow (RM) is often the primary organ at risk in radioimmunotherapy; irradiation of marrow may induce short- and long-term hematologic toxicity. ¹⁷⁷Lu-lilotomab satetraxetan is a novel anti-CD37 antibody-radionuclide conjugate currently in phase 1/2a. Two predosing regimens have been investigated, one with 40 mg of unlabeled lilotomab antibody (arm 1) and one without (arm 2). The aim of this work was to compare RM-absorbed doses for the two arms and to correlate absorbed doses with hematologic toxicity. Eight patients with relapsed CD37+ indolent B-cell non-Hodgkin lymphoma were included for RM dosimetry. Hybrid SPECT and CT images were used to estimate the activity concentration in the RM of L2-L4. Pharmacokinetic parameters were calculated after measurement of the ¹⁷⁷Lu-lilotomab satetraxetan concentration in blood samples. Adverse events were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. The mean absorbed doses to RM were 0.9 mGy/MBq for arm 1 (lilotomab+) and 1.5 mGy/MBq for arm 2 (lilotomab-). There was a statistically significant difference between arms 1 and 2 (Student t test, P = 0.02). Total RM-absorbed doses ranged from 67 to 127 cGy in arm 1 and from 158 to 207 cGy in arm 2. For blood, the area under the curve was higher with lilotomab predosing than without (P = 0.001), whereas the volume of distribution and the clearance of ¹⁷⁷Lu-lilotomab satetraxetan was significantly lower (P = 0.01 and P = 0.03, respectively). Patients with grade 3/4 thrombocytopenia had received significantly higher radiation doses to RM than patients with grade 1/2 thrombocytopenia (P = 0.02). A surrogate, non-imaging-based, method underestimated the RM dose and did not show any correlation with toxicity. Predosing with lilotomab reduces the RM-absorbed dose for ¹⁷⁷Lu-lilotomab satetraxetan patients. The decrease in RM dose could be explained by the lower volume of distribution. Hematologic toxicity was more severe for patients receiving higher absorbed radiation doses, indicating that adverse events possibly can be predicted by the calculation of absorbed dose to RM from SPECT/CT images.

Tumor-Absorbed Dose for Non-Hodgkin Lymphoma Patients Treated with the Anti-CD37 Antibody Radionuclide Conjugate 177Lu-Lilotomab Satetraxetan

Sun, 01 Jan 2017 00:00:00 +0000

¹⁷⁷Lu-lilotomab satetraxetan is a novel antibody radionuclide conjugate currently tested in a phase 1/2a first-in-human dosage escalation trial for patients with relapsed CD37+ indolent non-Hodgkin lymphoma. The aim of this work was to develop dosimetric methods and calculate tumor-absorbed radiation doses for patients treated with ¹⁷⁷Lu-lilotomab satetraxetan. Patients were treated at escalating injected activities (10, 15 and 20 MBq/kg) of ¹⁷⁷Lu-lilotomab satetraxetan and with different predosing, with or without 40 mg of unlabeled lilotomab. Eight patients were included for the tumor dosimetry study. Tumor radioactivity concentrations were calculated from SPECT acquisitions at multiple time points, and tumor masses were delineated from corresponding CT scans. Tumor-absorbed doses were then calculated using the OLINDA sphere model. To perform voxel dosimetry, the SPECT/CT data and an in-house-developed MATLAB program were combined to investigate the dose rate homogeneity. Twenty-six tumors in 8 patients were ascribed a mean tumor-absorbed dose. Absorbed doses ranged from 75 to 794 cGy, with a median of 264 cGy across different dosage levels and different predosing. A significant correlation between the dosage level and tumor-absorbed dose was found. Twenty-one tumors were included for voxel dosimetry and parameters describing dose-volume coverage calculated. The investigation of intratumor voxel doses indicates that mean tumor dose is correlated to these parameters. Tumor-absorbed doses for patients treated with ¹⁷⁷Lu-lilotomab satetraxetan are comparable to doses reported for other radioimmunotherapy compounds. Although the intertumor variability was considerable, a correlation between tumor dose and patient dosage level was found. Our results indicate that mean dose may be used as the sole dosimetric parameter on the lesion level.