Visualization of Receptor-Interacting Protein Kinase 1 (RIPK1) by Brain Imaging with Positron Emission Tomography
Year: 2021
Type: article
Abstract: 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.
Source: Journal of Medicinal Chemistry
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Aging Promotes Pain Chronification through Changes in PGC-1alpha Expression and Interneuron Dysfunction, Characterizing the roles of novel soluble GSMs in AD pathology., Carbon-11 Automation Equipment for Human PET Radiotracer Production, Development and Validation of a Clinically Relevant Animal Pain Model, Development and Validation of a Clinically Relevant Animal Pain Model, Gut Microbiota Influences Postoperative Cognitive Dysfunction through Indole-3-Propionic Acid, Molecular imaging of RIPK1/necroptosis as a key biomarker in Alzheimer's disease, Gut Microbiota Underlies the Heterogeneity of Aging Brain's Susceptibility to Postoperative Delirium, G9000343202
OpenAlex ID: W3205867498