In Vivo Testing of 177Lu-Labelled Anti-PSMA Antibody as a New Radioimmunotherapeutic Agent Against Prostate Cancer

摘要

Aim: The goal of the present study was to test the 177Lu-labelled anti-PSMA monoclonal antibody 3/F11 (177Lu-DOTA-3/F11) as a new radioimmunotherapeutic agent in a prostate cancer SCID mouse xenograft model. Materials and Methods: The mAb 3/F11 was 177Lu labelled using 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) as chelating agent. DOTA-3/F11 was tested for cell binding and serum immunoreactivity by flow cytometry. The biodistribution and the therapeutic efficacy of 177Lu-DOTA-3/F11 in mice bearing PSMA-positive C4-2 prostate cancer xenografts were evaluated. Results: 3/F11 and DOTA-3/F11 showed high and specific cell binding and similar serum half-lives of approximately seven days. Biodistribution studies revealed an increasing tumour uptake of 177Lu DOTA-3/F11 over time with maximum tumour-to-muscle and tumour-to-blood ratios after 72 h. A single dose of 1 MBq 177Lu-DOTA-3/F11 inhibited tumour growth and prolonged survival. Conclusion: This study indicated that 177Lu-DOTA-3/F11 may be a suitable radioimmunotherapeutic agent for the treatment of prostate cancer.