Preclinical development of a novel [68Ga]Ga-/[177Lu]Lu-labeled agent for PSMA-targeted imaging and therapy

Prostate-specific membrane antigen (PSMA)-targeted radiolabeled agents have been developed to diagnose and treat prostate cancer. In this study, we developed a novel 68 Ga-/ 177 Lu-labeled PSMA-targeted agent for potential for theranostics of prostate cancer. Methods:[ 68 Ga]Ga-/[ 177 Lu]Lu-PSMA-BP were efficiently prepared manually. For in vitro cell experiments 22Rv1 (PSMA+) and PC-3 (PSMA-) cell lines were used. Biodistribution studies, small-animal SPECT imaging, Micro-PET imaging, and therapy studies of [ 68 Ga]Ga-/[ 177 Lu]Lu-PSMA-BP were conducted in mice bearing 22Rv1 and PC-3 xenografted tumors. Results:[ 68 Ga]Ga-/[ 177 Lu]Lu-PSMA-BP were prepared within 30 min. The binding affinity Ki value of PSMA-BP to PSMA was 8.34 ± 2.02 nM. Micro-PET and small-animal SPECT imaging showed accumulation of [ 68 Ga]Ga-/[ 177 Lu]Lu-PSMA-BP mainly in 22Rv1 tumors with a favorable clearance pattern from non-target oragans. Low radioactivity accumulation was observed in PC-3 tumors and PSMA-expressing tissues. The SUVmax for 22Rv1 tumor, PC-3 tumor were 0.77 ± 0.16, 0.09 ± 0.07. The uptake of 68 Ga-PSMA-BP in 22Rv1 tumors could be substantially blocked by 2-PMPA (− 81.82%). The mice treated with either low or high dose of 177 Lu-PSMA-BP showed delayed tumor growth. Conclusion: Our results demonstrated the promising theranostic potential of [ 68 Ga]Ga-/[ 177 Lu]Lu-PSMA-BP for prostate cancer, while the efficacy warranted further investigation to evaluate the potential for clinical application. Graphical abstract