| Literature DB >> 34652135 |
Yu Lan1,2, Ping Bai1, Yan Liu1, Sepideh Afshar3, Robin Striar1, Anna Kathryn Rattray1, Tyler Nicholas Meyer1, Amelia G Langan1, Alisa M Posner1, Shiqian Shen4, Rudolph E Tanzi5, Can Zhang5, Changning Wang1.
Abstract
We report the development of the first positron emission tomography (PET) radiotracer, [18F]CNY-07, based on a highly specific and potent RIPK1 inhibitor, Nec-1s, for RIPK1/necroptosis brain imaging in rodents. [18F]CNY-07 was synthesized through copper-mediated 18F-radiolabeling from an aryl boronic ester precursor and studied in vivo PET imaging in rodents. PET imaging results showed that [18F]CNY-07 can penetrate the blood-brain barrier with a maximum percent injected dose per unit volume of 3 at 10 min postinjection in the brain in vivo. Self-blocking studies of [18F]CNY-07 by pretreating with unlabeled molecules in rodents showed reduced radioactivity in animal brains (30% radioactivity decreased), indicating the binding specificity of our radiotracer. Our studies demonstrate that [18F]CNY-07 has provided a useful PET radioligand enabling brain RIPK1 imaging, which could be a valuable research tool in studying RIPK1-related neurological disorders in animals and potentially humans.Entities:
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Year: 2021 PMID： 34652135 PMCID： PMC8858444 DOI： 10.1021/acs.jmedchem.1c01477
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 8.039