Damian Wild1, Melpomeni Fani2, Richard Fischer4, Luigi Del Pozzo4, Felix Kaul2, Simone Krebs4, Richard Fischer4, Jean E F Rivier5, Jean Claude Reubi6, Helmut R Maecke7, Wolfgang A Weber8. 1. Department of Nuclear Medicine, University Hospital Freiburg, Freiburg, Germany Division of Nuclear Medicine, University of Basel Hospital, Basel, Switzerland damian.wild@usb.ch. 2. Department of Nuclear Medicine, University Hospital Freiburg, Freiburg, Germany Division of Nuclear Medicine, University of Basel Hospital, Basel, Switzerland. 3. Oncology "Dreiländereck," Lörrach, Germany. 4. Department of Nuclear Medicine, University Hospital Freiburg, Freiburg, Germany. 5. Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, California. 6. Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, Berne, Switzerland. 7. Department of Nuclear Medicine, University Hospital Freiburg, Freiburg, Germany German Cancer Consortium (DKTK), Freiburg, Germany; and. 8. Department of Nuclear Medicine, University Hospital Freiburg, Freiburg, Germany German Cancer Consortium (DKTK), Freiburg, Germany; and Department of Radiology, Sloan-Kettering Cancer Center, New York, New York.
Abstract
UNLABELLED: Preclinical and clinical studies have indicated that somatostatin receptor (sst)-expressing tumors demonstrate higher uptake of radiolabeled sst antagonists than of sst agonists. In 4 consecutive patients with advanced neuroendocrine tumors, we evaluated whether treatment with (177)Lu-labeled sst antagonists is feasible. METHODS: After injection of approximately 1 GBq of (177)Lu-DOTA-[Cpa-c(DCys-Aph(Hor)-DAph(Cbm)-Lys-Thr-Cys)-DTyr-NH2] ((177)Lu-DOTA-JR11) and (177)Lu-DOTATATE, 3-dimensional voxel dosimetry analysis based on SPECT/CT was performed. A higher tumor-to-organ dose ratio for (177)Lu-DOTA-JR11 than for (177)Lu-DOTATATE was the prerequisite for treatment with (177)Lu-DOTA-JR11. RESULTS: Reversible minor adverse effects of (177)Lu-DOTA-JR11 were observed. (177)Lu-DOTA-JR11 showed a 1.7-10.6 times higher tumor dose than (177)Lu-DOTATATE. At the same time, the tumor-to-kidney and tumor-to-bone marrow dose ratio was 1.1-7.2 times higher. All 4 patients were treated with (177)Lu-DOTA-JR11, resulting in partial remission in 2 patients, stable disease in 1 patient, and mixed response in the other patient. CONCLUSION: Treatment of neuroendocrine tumors with radiolabeled sst antagonists is clinically feasible and may have a significant impact on peptide receptor radionuclide therapy.
UNLABELLED: Preclinical and clinical studies have indicated that somatostatin receptor (sst)-expressing tumors demonstrate higher uptake of radiolabeled sst antagonists than of sst agonists. In 4 consecutive patients with advanced neuroendocrine tumors, we evaluated whether treatment with (177)Lu-labeled sst antagonists is feasible. METHODS: After injection of approximately 1 GBq of (177)Lu-DOTA-[Cpa-c(DCys-Aph(Hor)-DAph(Cbm)-Lys-Thr-Cys)-DTyr-NH2] ((177)Lu-DOTA-JR11) and (177)Lu-DOTATATE, 3-dimensional voxel dosimetry analysis based on SPECT/CT was performed. A higher tumor-to-organ dose ratio for (177)Lu-DOTA-JR11 than for (177)Lu-DOTATATE was the prerequisite for treatment with (177)Lu-DOTA-JR11. RESULTS: Reversible minor adverse effects of (177)Lu-DOTA-JR11 were observed. (177)Lu-DOTA-JR11 showed a 1.7-10.6 times higher tumor dose than (177)Lu-DOTATATE. At the same time, the tumor-to-kidney and tumor-to-bone marrow dose ratio was 1.1-7.2 times higher. All 4 patients were treated with (177)Lu-DOTA-JR11, resulting in partial remission in 2 patients, stable disease in 1 patient, and mixed response in the other patient. CONCLUSION: Treatment of neuroendocrine tumors with radiolabeled sst antagonists is clinically feasible and may have a significant impact on peptide receptor radionuclide therapy.
Authors: Andreas Delker; Wolfgang Peter Fendler; Clemens Kratochwil; Anika Brunegraf; Astrid Gosewisch; Franz Josef Gildehaus; Stefan Tritschler; Christian Georg Stief; Klaus Kopka; Uwe Haberkorn; Peter Bartenstein; Guido Böning Journal: Eur J Nucl Med Mol Imaging Date: 2015-08-29 Impact factor: 9.236
Authors: Giuseppe Lo Russo; Sara Pusceddu; Natalie Prinzi; Martina Imbimbo; Claudia Proto; Diego Signorelli; Milena Vitali; Monica Ganzinelli; Marco Maccauro; Roberto Buzzoni; Ettore Seregni; Filippo de Braud; Marina Chiara Garassino Journal: Tumour Biol Date: 2016-07-27