High Contrast PET Imaging of GRPR Expression in Prostate Cancer Using Cobalt-Labeled Bombesin Antagonist RM26

Abstract

High gastrin releasing peptide receptor (GRPR) expression is associated with numerous cancers including prostate and breast cancer. The aim of the current study was to develop a ⁵⁵Co-labeled PET agent based on GRPR antagonist RM26 for visualization of GRPR-expressing tumors. Labeling with ⁵⁷Co and ⁵⁵Co, stability, binding specificity, and in vitro and in vivo characteristics of ⁵⁷Co-NOTA-PEG₂-RM26 were studied. NOTA-PEG₂-RM26 was successfully radiolabeled with ⁵⁷Co and ⁵⁵Co with high yields and demonstrated high stability. The radiopeptide showed retained binding specificity to GRPR in vitro and in vivo. ⁵⁷Co-NOTA-PEG₂-RM26 biodistribution in mice was characterized by rapid clearance of radioactivity from blood and normal non-GRPR-expressing organs and low hepatic uptake. The clearance was predominantly renal with a low degree of radioactivity reabsorption. Tumor-to-blood ratios were approximately 200 (3 h pi) and 1000 (24 h pi). The favorable biodistribution of cobalt-labeled NOTA-PEG₂-RM26 translated into high contrast preclinical PET/CT (using ⁵⁵Co) and SPECT/CT (using ⁵⁷Co) images of PC-3 xenografts. The initial biological results suggest that ⁵⁵Co-NOTA-PEG₂-RM26 is a promising tracer for PET visualization of GRPR-expressing tumors.