Development and characterization of a 177Lu-labeled anti-prostate stem cell antigen (PSCA) monoclonal antibody for metastatic prostate cancer

The clinical need of new therapeutics for advanced prostate cancer is continuingly high because there still exist no curative treatment options. It has been shown that especially targeted therapies using radionuclides gives enhanced specificity and increased overall survival of prostate cancer patients. Antibodies represent attractive transport vehicles for the delivery of radionuclides to prostate cancer cells for several reasons, such as: metastatic site location and small volume disease. Here, we describe the development and characterization of a novel 177Lu-labeled antibody-conjugate that offers encouraging features to be used for the therapy PSCA-expressing prostate tumors. The PSCA is a cell surface antigen that is present in nearly all primary prostate tumors and further upregulated in many bone and lymph node metastases. Therefore, it is proposed as a promising tumor target structure for both, therapy and diagnosis, of prostate cancer. Purified PSCA-directed antibody demonstrated a high specificity and affinity, with dissociation constant of 10 nM to PC3-PSCA cells. The antibody was conjugated with, on average, three CHX-A’’-DTPA molecules, as verified by MALDI-TOF analysis. Subsequent radiolabeling of the antibody-chelator-conjugate with Lutetium-177 could be performed at high radiochemical purity (>95%, radio HPLC) while preserving binding properties to the PSCA. SPECT scanning with the 177Lu-labeled antibody-conjugate was used to investigate the targeting potential in mice with established PSCA-expressing tumors. The outcome was the production of excellent high contrast images from 3 to 170 h post injection. With these promising results, we next want to evaluate the antitumor activity in vivo.