In vivo and in vitro evaluation of 64 CU-labeled bombesin analogs for targeting gastrin-releasing peptide receptors on human prostate cancer [abstract]

Abstract

Introduction: Gastrin-releasing peptide receptors (GRPr) are expressed in high numbers on human prostate cancer. The bombesin peptide derivative, BBN(7- 14)NH2, has high affinity and selectivity to GRPr. Therefore, Copper-64 (64Cu) radiolabeled bombesin conjugates could have potential in positron-emission tomography (PET) of human prostate cancer. Methods: In vitro assays of the NO2A bombesin conjugates and non-radioactive 63Cu-NO2A bombesin conjugates were performed in human PC-3 cells. In vivo pharmacokinetic studies of the radiolabeled 64Cu-NO2A bombesin conjugates were performed in normal CF-1 and PC-3 tumor-bearing SCID mice. In vivo, multimodal, molecular images were obtained of the radiolabeled 64Cu-NO2A bombesin conjugates in PC-3 tumor-bearing SCID mice via microPET/CT. Results: In vitro studies indicated idea uptake of the NO2A bombesin conjugates (1.99-6.24 nM), and 63Cu-NO2A bombesin conjugates (3.16-51.81 nM) in PC-3 cells. In vivo results of the 64Cu-NO2A bombesin conjugates at 1, 4, and 24 h p.i. showed affinity towards GRPr-positive tissue and effective clearance properties. Due to the favorable in vivo pharmacokinetic properties of 64Cu-NO2A bombesin conjugates, high-resolution multimodal, molecular imaging was performed via microPET/CT in aPC-3 tumor-bearing SCID mouse model. High-quality target to non-target images were obtained, with the tumors clearly visible. Conclusions: The 64Cu-NO2A bombesin conjugates showed affinity and specificity towards GRPr-positive tissues. High quality microPET images of PC-3 xenografted tumors in SCID mouse model were obtained, demonstrating the potential for PET imaging of GRPr-positive human prostate cancer tumors.