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Synthesis and evaluation of a68Ga-labeled bradykinin B1 receptor agonist for imaging with positron emission tomography
A novel68Ga-labeled bradykinin B1 receptor (B1R) agonist,68Ga-Z01115, was synthesized and evaluated for imaging with positron emission tomography (PET). Z01115 exhibited good binding affinity (Ki= 25.4 ¡À 5.1 nM) to hB1R.68Ga-Z01115 was prepared in 74 ¡À 5 decay-corrected radiochemical yield with >99% radiochemical purity and 155 ¡À 89 GBq/mumol (4.2 ¡À 2.4 Ci/mumol) specific activity.68Ga-Z01115 was stable in vitro in mouse plasma (93% remaining intact after 60 min incubation), and relatively stable in vivo (51 ¡À 5% remaining intact at 5 min post-injection). PET imaging and biodistribution studies in mice showed that68Ga-Z01115 cleared rapidly from nontarget tissues/organs, and generated high target-to-nontarget contrast images. The uptake of68Ga-Z01115 in B1R-positive (B1R+) tumor was 5.65 ¡À 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 of68Ga-Z01115 in B1R+ tumors was reduced by ?90% with co-injection of cold standard, confirming it was mediated by B1R. Our data suggest that68Ga-Z01115 is a promising tracer for imaging the expression of B1R that is overexpressed in a variety of cancers.
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Reference£º
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI