Synthesis and evaluation of a 68Ga-labeled bradykinin B1 receptor agonist for imaging with positron emission tomography

A novel Ga-68-labeled bradykinin B1 receptor (B1R) agonist, Ga-68-Z01115, was synthesized and evaluated for imaging with positron emission tomography (PET). Z01115 exhibited good binding affinity (K-i = 25.4 +/- 5.1 nM) to hB1R. Ga-68-Z01115 was prepared in 74 +/- 5 decay-corrected radiochemical yield with >99% radiochemical purity and 155 +/- 89 GBq/mu mol (4.2 +/- 2.4 Ci/mu mol) specific activity. Ga-68-Z01115 was stable in vitro in mouse plasma (93% remaining intact after 60 min incubation), and relatively stable in vivo (51 +/- 5% remaining intact at 5 min post-injection). PET imaging and biodistribution studies in mice showed that Ga-68-Z01115 cleared rapidly from nontarget tissues/organs, and generated high target-to-nontarget contrast images. The uptake of Ga-68-Z01115 in B1R-positive (B1R+) tumor was 5.65 +/- 0.59%ID/g at 1 h post-injection. Average contrast ratios of B1R+ tumor-to-B1R- tumor, -to-blood and -to-muscle were 24.3, 24.4 and 82.9, respectively. Uptake of Ga-68-Z01115 in SIR+ tumors was reduced by similar to 90% with co-injection of cold standard, confirming it was mediated by B1R. Our data suggest that Ga-68-Z01115 is a promising tracer for imaging the expression of B1R that is overexpressed in a variety of cancers. (C) 2016 Elsevier Ltd. All rights reserved.