Synthesis and evaluation of a 68Ga-labeled bradykinin B1 receptor agonist for imaging with positron emission tomography. Issue 2 (15th January 2017)

• Record Type: Journal Article
• Authors: Amouroux, Guillaume; Zhang, Zhengxing; Pan, Jinhe; Jenni, Silvia; Zhang, Chengcheng; Hundal-Jabal, Navjit; Colpo, Nadine; Zeisler, Jutta; Lin, Kuo-Shyan; Bénard, François
• Is Part Of: Bioorganic & medicinal chemistry. Volume 25:Issue 2(2017)
• Page Start: 690
• Page End: 696
• Publication Date: 2017-01-15
• Subjects: Bradykinin B1 receptor -- Agonist -- Antagonist -- Positron emission tomography -- Gallium-68; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2016.11.038
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: A novel 68 Ga-labeled bradykinin B1 receptor (B1R) agonist, 68 Ga-Z01115, was synthesized and evaluated for imaging with positron emission tomography (PET). Z01115 exhibited good binding affinity (Ki = 25.4 ± 5.1 nM) to hB1R. 68 Ga-Z01115 was prepared in 74 ± 5 decay-corrected radiochemical yield with >99% radiochemical purity and 155 ± 89 GBq/µmol (4.2 ± 2.4 Ci/μmol) specific activity. 68 Ga-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 68 Ga-Z01115 cleared rapidly from nontarget tissues/organs, and generated high target-to-nontarget contrast images. The uptake of 68 Ga-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 68 Ga-Z01115 in B1R+ tumors was reduced by ∼90% with co-injection of cold standard, confirming it was mediated by B1R. Our data suggest that 68 Ga-Z01115 is a promising tracer for imaging the expression of B1R that is overexpressed in a variety of cancers.