https://www.theragnostics.no/en/author/jon-erik-holtedahl/ Jon Erik Holtedahl Hugo Blox Builder (https://hugoblox.com)en-usSun, 01 Apr 2018 00:00:00 +0000 https://www.theragnostics.no/media/icon_hu14557955862192370321.png https://www.theragnostics.no/en/author/jon-erik-holtedahl/ https://www.theragnostics.no/en/publications/blakkisrud-2018-biodistribution/ Sun, 01 Apr 2018 00:00:00 +0000 https://www.theragnostics.no/en/publications/blakkisrud-2018-biodistribution/ <hr> <p>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.</p> <p><strong>Methods:</strong> 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.</p> <p><strong>Results:</strong> 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.</p> <p><strong>Conclusion:</strong> 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.</p> https://www.theragnostics.no/en/publications/kristian-2017-dynamic/ Sat, 01 Apr 2017 00:00:00 +0000 https://www.theragnostics.no/en/publications/kristian-2017-dynamic/ <hr> <p>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.</p>