Prospects of medium specific activity 177Lu in targeted therapy of prostate cancer using 177Lu-labeled PSMA inhibitor

• Published in: Journal of labelled compounds & radiopharmaceuticals Vol. 59; no. 9; pp. 364 - 371
• Main Authors: Chakraborty, Sudipta, Chakravarty, Rubel, Shetty, Priyalata, Vimalnath, K. V., Sen, Ishita B., Dash, Ashutosh
• Format: Journal Article
• Language: English; French; German
• Published: Bognor Regis Blackwell Publishing Ltd 01-07-2016; Wiley Subscription Services, Inc
• Subjects: 177Lu; prostate cancer; PSMA-617; specific activity; targeted radionuclide therapy; therapeutic dose
• ISSN: 0362-4803; 1099-1344
• DOI: 10.1002/jlcr.3414

Targeted radionuclide therapy using 177Lu‐labeled peptidomimetic inhibitor of prostate specific membrane antigen (PSMA) viz. PSMA‐617 is emerging as one the most effective strategies for management of metastatic prostate cancer, which is one of the leading causes of cancer related death. The aim of the present study is to develop a robust and easily adaptable protocol for formulation of therapeutic dose of 177Lu‐PSMA‐617 at hospital radiopharmacy using moderate specific activity 177Lu available at an affordable cost. Extensive radiochemical studies were performed to optimize the required [PSMA‐617] / [Lu] ratio and other parameters to formulate 7.4 GBq dose of 177Lu‐PSMA‐617. Based on these, 7.4 GBq therapeutic dose of 177Lu‐PSMA‐617 was formulated by incubating 160 µg of PSMA‐617 with indigenously produced 177LuCl3 (555 GBq/µg specific activity of 177Lu) at 90 °C for 30 min. The radiochemical purity of the formulation was 98.3 ± 0.6% (n = 7) which was retained to the extent of >95% after 7 d in normal saline at room temperature and >96% after 2 d in human serum at 37 °C. Preliminary clinical studies showed specific targeting of the agent in the lesion sites and similar physiological distribution as in diagnostic 68Ga‐PSMA‐11 PET scans performed earlier. The developed optimized protocol for formulating therapeutic dose of 177Lu‐PSMA‐617 could be useful for large number of nuclear medicine therapy clinics across the world having access to moderate specific activity 177Lu at an affordable cost.
Targeted Radionuclide Therapy of Prostate Cancer using 177Lu‐labeled PSMA inhibitor: Prospects of Large‐scale Utilization of 177Lu Produced in a Medium Flux Research Reactor via Direct Neutron Activation Route