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

• Published in: Journal of labelled compounds & radiopharmaceuticals 2016-07, Vol.59 (9), p.364-371
• Main Authors: Chakraborty, Sudipta, Chakravarty, Rubel, Shetty, Priyalata, Vimalnath, K V, Sen, Ishita B, Dash, Ashutosh
• Format: Article
• Language: English
• Subjects: Aged; Antigens, Surface - metabolism; Dipeptides - chemistry; Dipeptides - metabolism; Dipeptides - pharmacology; Dipeptides - therapeutic use; Drug Stability; Glutamate Carboxypeptidase II - antagonists & inhibitors; Glutamate Carboxypeptidase II - metabolism; Heterocyclic Compounds, 1-Ring - chemistry; Heterocyclic Compounds, 1-Ring - metabolism; Heterocyclic Compounds, 1-Ring - pharmacology; Heterocyclic Compounds, 1-Ring - therapeutic use; Humans; Lutetium - therapeutic use; Male; Middle Aged; Positron-Emission Tomography; Prostatic Neoplasms - diagnostic imaging; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - radiotherapy; Quality Control; Radiochemistry; Radioisotopes
• ISSN: 1099-1344
• DOI: 10.1002/jlcr.3414

Targeted radionuclide therapy using (177) Lu-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 (177) Lu-PSMA-617 at hospital radiopharmacy using moderate specific activity (177) Lu 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 (177) Lu-PSMA-617. Based on these, 7.4 GBq therapeutic dose of (177) Lu-PSMA-617 was formulated by incubating 160 µg of PSMA-617 with indigenously produced (177) LuCl3 (555 GBq/µg specific activity of (177) Lu) 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 (68) Ga-PSMA-11 PET scans performed earlier. The developed optimized protocol for formulating therapeutic dose of (177) Lu-PSMA-617 could be useful for large number of nuclear medicine therapy clinics across the world having access to moderate specific activity (177) Lu at an affordable cost.