Development of a 68Ga-Labeled Bombesin Analog for Gastrin-ReleasingPeptide Receptor-Expressing Prostate Tumor Imaging

Our previous study demonstrated the therapeutic efficacy of 177Lu-DOTA-gluBBN for the treatment of GRPRexpressing prostate tumors. As a matched pair for 177Lu, the development of labeling and molecular imaging technology using 68Ga is needed to introduce the “theranostic” approach. Therefore, the present study described the 68Ga-labeled bombesin analog, 68Ga-DOTA-gluBBN for the imaging of GRPR-expressing prostate tumors. Methods: 68Ga was concentrated and labeled with DOTA-gluBBN using the NaCl method, and the labeling yield was evaluated by iTLC-SG. Human prostate PC-3 tumor cells were used to induce a subcutaneously xenografted-tumor model and a peritoneal metastasized tumor model. PET-CT imaging studies were performed in both animal models. Results: Eluted 68Ga solution containing 5~10% of impurities was purified (>99%) and labeled with DOTA-gluBBN with a high incorporation yield (>98%). The total preparation time from the elution and quality control steps required below twenty minutes. 68Ga-DOTA-gluBBN was clearly visualized in xenografted PC-3 tumors at 1 hr p.i., and the tumor-tomuscle ratio was 1.7-fold higher than that observed using 18F-FDG. In a peritoneal metastasized tumor model, PC-3 tumors were widespread in peritoneum. The metastases could not be specifically visualized by PET imaging, but the tumor uptake was confirmed by ex-vivo autoradiography. Conclusion: Favorable preclinical results demonstrating specific and effective imaging of GRPR-expressing prostate tumor recommend the further evaluation of 68Ga-DOTA-gluBBN in a clinical study to introduce a theranostic approach for prostate carcinoma patients.