Visualization of Receptor-Interacting Protein Kinase 1 (RIPK1) by Brain Imaging with Positron Emission Tomography

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.