Preclinical Characterization of the 177Lu-Labeled Prostate Stem Cell Antigen (PSCA)-Specific Monoclonal Antibody 7F5

Prostate specific membrane antigen (PSMA) is an excellent target for imaging and treatment of prostate carcinoma (PCa). Unfortunately, not all PCa cells express PSMA. Therefore, alternative theranostic targets are required. The membrane protein prostate stem cell antigen (PSCA) is highly overexpressed in most primary prostate carcinoma (PCa) cells and in metastatic and hormone refractory tumor cells. Moreover, PSCA expression positively correlates with tumor progression. Therefore, it represents a potential alternative theranostic target suitable for imaging and/or radioimmunotherapy. In order to support this working hypothesis, we conjugated our previously described anti-PSCA monoclonal antibody (mAb) 7F5 with the bifunctional chelator CHX-A ''-DTPA and subsequently radiolabeled it with the theranostic radionuclide Lu-177. The resulting radiolabeled mAb ([Lu-177]Lu-CHX-A ''-DTPA-7F5) was characterized both in vitro and in vivo. It showed a high radiochemical purity (>95%) and stability. The labelling did not affect its binding capability. Biodistribution studies showed a high specific tumor uptake compared to most non-targeted tissues in mice bearing PSCA-positive tumors. Accordingly, SPECT/CT images revealed a high tumor-to-background ratios from 16 h to 7 days after administration of [Lu-177]Lu-CHX-A ''-DTPA-7F5. Consequently, [Lu-177]Lu-CHX-A ''-DTPA-7F5 represents a promising candidate for imaging and in the future also for radioimmunotherapy.

Automated summary

Prostate specific membrane antigen (PSMA) is a promising target for imaging and treatment of prostate carcinoma (PCa), but alternative targets are needed. Prostate stem cell antigen (PSCA) is highly overexpressed in most PCa cells and correlates with tumor progression, making it a potential alternative target for theranostics. The radiolabeled antibody [Lu-177]Lu-CHX-A ''-DTPA-7F5 showed high tumor uptake and specificity in mice bearing PSCA-positive tumors, indicating its potential for imaging and radioimmunotherapy.