Positron Emission Tomography Imaging of Prostate Cancer with Ga-68-Labeled Gastrin-Releasing Peptide Receptor Agonist BBN(7–14) and Antagonist RM26

[Image: see text] Radiolabeled bombesin (BBN) analogs have long been used for developing gastrin-releasing peptide receptor (GRPR) targeted imaging probes, and tracers with excellent in vivo performance including high tumor uptake, high contrast, and favorable pharmacokinetics are highly desired. In this study, we compared the (68)Ga-labeled GRPR agonist (Gln–Trp–Ala–Val–Gly–His–Leu–Met–NH(2), BBN(7–14)) and antagonist (d-Phe–Gln–Trp–Ala–Val–Gly–His–Sta–Leu–NH(2), RM26) for the positron emission tomography (PET) imaging of prostate cancer. The in vitro stabilities, receptor binding, cell uptake, internalization, and efflux properties of the probes (68)Ga–1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)–Aca–BBN(7–14) and (68)Ga–NOTA–poly(ethylene glycol)(3) (PEG(3))–RM26 were studied in PC-3 cells, and the in vivo GRPR targeting abilities and kinetics were investigated using PC-3 tumor xenografted mice. BBN(7–14), PEG(3)-RM26, NOTA–Aca–BBN(7–14), and NOTA–PEG(3)–RM26 showed similar binding affinity to GRPR. In PC-3 tumor-bearing mice, the tumor uptake of (68)Ga–NOTA–PEG(3)–RM26 remained at around 3.00 percentage of injected dose per gram of tissue within 1 h after injection, in contrast with (68)Ga–NOTA–Aca–BBN(7–14), which demonstrated rapid elimination and high background signal. Additionally, the majority of the (68)Ga–NOTA–PEG(3)–RM26 remained intact in mouse serum at 5 min after injection, while almost all of the (68)Ga–NOTA–Aca–BBN(7–14) was degraded under the same conditions, demonstrating more-favorable in vivo pharmacokinetic properties and metabolic stabilities of the antagonist probe relative to its agonist counterpart. Overall, the antagonistic GRPR targeted probe (68)Ga–NOTA–PEG(3)–RM26 is a more-promising candidate than the agonist (68)Ga–NOTA–Aca–BBN(7–14) for the PET imaging of prostate cancer patients.