Tapas Das1, Mohini Guleria2, Anil Parab3, Chanchala Kale3, Hina Shah3, Haladhar D Sarma4, Vikram R Lele3, Sharmila Banerjee5. 1. Radiopharmaceuticals Chemistry Section, Radiochemistry and Isotope Group, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085, India; Homi Bhabha National Institute, Anushaktinagar, Mumbai 400 094, India. Electronic address: tdas@barc.gov.in. 2. Radiopharmaceuticals Chemistry Section, Radiochemistry and Isotope Group, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085, India. 3. Department of Nuclear Medicine, Jaslok Hospital and Research Centre, Mumbai 400 026, India. 4. Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085, India. 5. Radiopharmaceuticals Chemistry Section, Radiochemistry and Isotope Group, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085, India; Homi Bhabha National Institute, Anushaktinagar, Mumbai 400 094, India. Electronic address: sharmila@barc.gov.in.
Abstract
OBJECTIVE: PSMA-617 is reported to exhibit very high binding affinity towards PSMA receptors, over-expressed on prostate cancer cells and therefore, (177)Lu-labeled PSMA-617 is expected to play a pivotal role in the clinical management of patients suffering from ca prostate. The objective of the present study is to formulate the patient dose of (177)Lu-labeled PSMA-617, pre-clinical studies in animal model and clinical investigation in limited number of prostate cancer patients as well evaluating its potential for theranostic application. EXPERIMENTAL: Patient dose of 7.4 GBq (200 mCi) of (177)Lu-labeled PSMA-617 was prepared by incubating 100 μg of PSMA-617 with (177)LuCl3 at 95 °C for 15 minutes. Radiochemical purity as well as in-vitro stability of the preparation was determined by PC and HPLC methods. The pharmacokinetic behavior and in-vivo distribution of the agent were studied by carrying out biodistribution studies in normal male Wistar rats. Preliminary clinical investigation was performed in 7 patients suffering from prostate cancer. RESULTS: The complex was prepared with >98% radiochemical purity under the optimized reaction protocols and the preparation exhibited adequate in-vitro stability. Biodistribution studies revealed no significant uptake in any of the major organ/tissue along with major clearance through renal pathway. Clinical studies showed similar distribution in lesions and physiologic areas of uptake as seen in diagnostic (68)Ga-PSMA-11 PET scans performed earlier. CONCLUSION: Preliminary clinical studies indicated the promising potential of the agent for theranostic applications. However, further investigations in large pool of patients are warranted to establish the theranostic potential of the agent.
OBJECTIVE:PSMA-617 is reported to exhibit very high binding affinity towards PSMA receptors, over-expressed on prostate cancer cells and therefore, (177)Lu-labeled PSMA-617 is expected to play a pivotal role in the clinical management of patients suffering from ca prostate. The objective of the present study is to formulate the patient dose of (177)Lu-labeled PSMA-617, pre-clinical studies in animal model and clinical investigation in limited number of prostate cancerpatients as well evaluating its potential for theranostic application. EXPERIMENTAL: Patient dose of 7.4 GBq (200 mCi) of (177)Lu-labeled PSMA-617 was prepared by incubating 100 μg of PSMA-617 with (177)LuCl3 at 95 °C for 15 minutes. Radiochemical purity as well as in-vitro stability of the preparation was determined by PC and HPLC methods. The pharmacokinetic behavior and in-vivo distribution of the agent were studied by carrying out biodistribution studies in normal male Wistar rats. Preliminary clinical investigation was performed in 7 patients suffering from prostate cancer. RESULTS: The complex was prepared with >98% radiochemical purity under the optimized reaction protocols and the preparation exhibited adequate in-vitro stability. Biodistribution studies revealed no significant uptake in any of the major organ/tissue along with major clearance through renal pathway. Clinical studies showed similar distribution in lesions and physiologic areas of uptake as seen in diagnostic (68)Ga-PSMA-11 PET scans performed earlier. CONCLUSION: Preliminary clinical studies indicated the promising potential of the agent for theranostic applications. However, further investigations in large pool of patients are warranted to establish the theranostic potential of the agent.
Authors: Christoph A Umbricht; Martina Benešová; Raffaella M Schmid; Andreas Türler; Roger Schibli; Nicholas P van der Meulen; Cristina Müller Journal: EJNMMI Res Date: 2017-01-19 Impact factor: 3.138