Johan Blakkisrud1, Jon Erik Holtedahl2,3, Ayca Løndalen4, Jostein Dahle5, Tore Bach-Gansmo4, Harald Holte6, Stine Nygaard6, Arne Kolstad6, Caroline Stokke2,7. 1. Department of Diagnostic Physics, Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway, and University of Oslo, Oslo, Norway johbla@ous-hf.no. 2. Department of Diagnostic Physics, Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway, and University of Oslo, Oslo, Norway. 3. Siemens Healthineers, Oslo, Norway. 4. Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway. 5. Nordic Nanovector ASA, Oslo, Norway. 6. Department of Oncology, Radiumhospitalet, Oslo University Hospital, Oslo, Norway; and. 7. Department of Life Sciences and Health, Oslo Metropolitan University, Oslo, Norway.
Abstract
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.
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.
Authors: Ken Herrmann; Markus Schwaiger; Jason S Lewis; Stephen B Solomon; Barbara J McNeil; Michael Baumann; Sanjiv S Gambhir; Hedvig Hricak; Ralph Weissleder Journal: Lancet Oncol Date: 2020-03 Impact factor: 41.316
Authors: Arne Kolstad; Tim Illidge; Nils Bolstad; Signe Spetalen; Ulf Madsbu; Caroline Stokke; Johan Blakkisrud; Ayca Løndalen; Noelle O'Rourke; Matthew Beasley; Wojciech Jurczak; Unn-Merete Fagerli; Michal Kaščák; Mike Bayne; Aleš Obr; Jostein Dahle; Lisa Rojkjaer; Veronique Pascal; Harald Holte Journal: Blood Adv Date: 2020-09-08