The radiolabeling of [161Tb]Tb-PSMA-617 by a novel radiolabeling method and preclinical evaluation by in vitro/in vivo methods

Prostate cancer (PC) is the most prevalent cancer in elderly men, exhibiting a positive correlation with age. As resistance to treatment has developed, particularly in the progressive stage of the disease and in the presence of microfocal multiple bone metastases, new generation radionuclide therapies have emerged. Recently introduced for treating micrometastatic foci, Terbium-161 ([ 161 Tb]) has shown great promise in prostate cancer treatment. This study investigated the in vitro and in vivo cytotoxicity of Terbium-161 ([ 161 Tb])-radiolabeled prostate-specific membrane antigen (PSMA)-617. [ 161 Tb]Tb-PSMA-617 (7.4 MBq/nmol) demonstrated a radiochemical yield of 97.99 ± 2.01% and hydrophilicity. [ 161 Tb]Tb-PSMA-617 was also shown to have good stability, with a radiochemical yield of over 95% up to 72 h. In vitro, [ 161 Tb]Tb-PSMA-617 exhibited cytotoxicity on LNCaP cells but not on PC3 cells. In vivo, scintigraphy imaging visualized the accumulation of [ 161 Tb]Tb-PSMA-617 in the prostate, kidneys, and bladder. The results suggest that [ 161 Tb]Tb-PSMA-617 can be an effective radiolabeled agent for the treatment of PSMA positive foci in prostate cancer.