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.

• Authors: Bogdan Mitran, Helge Thisgaard, Ulrika Rosenström, Johan Hygum Dam, Mats Larhed, Vladimir Tolmachev, Anna Orlova
• Journal: Contrast media & molecular imaging (Contrast Media Mol Imaging) Vol. 2017 Pg. 6873684 ( 2017) ISSN: 1555-4317 [Electronic] England
• PMID: 29097932 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cobalt Radioisotopes
• Receptors, Bombesin
• Bombesin

Topics

• Animals
• Bombesin (antagonists & inhibitors)
• Cobalt Radioisotopes (pharmacokinetics)
• Heterografts
• Humans
• Male
• Mice
• Positron-Emission Tomography (methods)
• Prostatic Neoplasms (diagnostic imaging)
• Receptors, Bombesin (analysis, antagonists & inhibitors, metabolism)
• Tissue Distribution