Lars Tore Gyland Mikalsen | Theragnostic Imaging

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.

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 .

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.

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.

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.

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