Identification of [18F]TRACK, a Fluorine-18-Labeled Tropomyosin Receptor Kinase (Trk) Inhibitor for PET Imaging.
Vadim Bernard-GauthierAndrew V MossineAnne MahringerArturo AliagaJustin J BaileyXia ShaoJenelle StauffJanna ArteagaPhillip ShermanMarilyn Grand'MaisonPierre-Luc RochonBjörn WänglerCarmen WänglerPeter BartensteinAlexey KostikovDavid R KaplanGert FrickerPedro Rosa-NetoPeter J H ScottRalf SchirrmacherPublished in: Journal of medicinal chemistry (2018)
Changes in expression and dysfunctional signaling of TrkA/B/C receptors and oncogenic Trk fusion proteins are found in neurological diseases and cancers. Here, we describe the development of a first 18F-labeled optimized lead suitable for in vivo imaging of Trk, [18F]TRACK, which is radiosynthesized with ease from a nonactivated aryl precursor concurrently combining largely reduced P-gp liability and improved brain kinetics compared to previous leads while displaying high on-target affinity and human kinome selectivity.
Keyphrases
- fluorescence imaging
- pet imaging
- positron emission tomography
- endothelial cells
- poor prognosis
- resting state
- binding protein
- cerebral ischemia
- white matter
- induced pluripotent stem cells
- high resolution
- pluripotent stem cells
- computed tomography
- tyrosine kinase
- functional connectivity
- protein kinase
- multiple sclerosis
- young adults
- subarachnoid hemorrhage
- structural basis