Open AccessVisualization of Receptor-Interacting Protein Kinase 1 (RIPK1) by Brain Imaging with Positron Emission Tomography
Author(s) -
Yu Lan,
Ping Bai,
Yan Liu,
Sepideh Afshar,
Robin Striar,
A Rattray,
Tyler Nicholas Meyer,
Amelia G. Langan,
Alisa M. Posner,
Shiqian Shen,
Rudolph E. Tanzi,
Can Zhang,
Changning Wang
Publication year - 2021
Publication title -
journal of medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.01
H-Index - 261
eISSN - 1520-4804
pISSN - 0022-2623
DOI - 10.1021/acs.jmedchem.1c01477
Subject(s) - chemistry , positron emission tomography , brain positron emission tomography , nuclear magnetic resonance , preclinical imaging , neuroscience , physics , psychology , genetics , biology , in vivo
We report the development of the first positron emission tomography (PET) radiotracer, [ 18 F]CNY-07, based on a highly specific and potent RIPK1 inhibitor, Nec-1s, for RIPK1/necroptosis brain imaging in rodents. [ 18 F]CNY-07 was synthesized through copper-mediated 18 F-radiolabeling from an aryl boronic ester precursor and studied in vivo PET imaging in rodents. PET imaging results showed that [ 18 F]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 [ 18 F]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 [ 18 F]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.