First-in-Human Brain Imaging of [18F]TRACK, a PET tracer for Tropomyosin Receptor Kinases

• Published in: ACS chemical neuroscience Vol. 10; no. 6; pp. 2697 - 2702
• Main Authors: Bailey, Justin J, Kaiser, Lena, Lindner, Simon, Wüst, Melinda, Thiel, Alexander, Soucy, Jean-Paul, Rosa-Neto, Pedro, Scott, Peter J. H, Unterrainer, Marcus, Kaplan, David R, Wängler, Carmen, Wängler, Björn, Bartenstein, Peter, Bernard-Gauthier, Vadim, Schirrmacher, Ralf
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 19.06.2019
• Subjects: copper-mediated radiofluorination; kinase inhibitor; fluorine-18; Tropomyosin receptor kinase; Trk; positron emission tomography; PET; neuroimaging
• ISSN: 1948-7193; 1948-7193
• DOI: 10.1021/acschemneuro.9b00144

The tropomyosin receptor kinase TrkA/B/C family is responsible for human neuronal growth, survival, and differentiation from early nervous system development stages onward. Downregulation of TrkA/B/C receptors characterizes numerous neurological disorders including Alzheimer’s disease (AD). Abnormally expressed Trk receptors or chimeric Trk fusion proteins are also well-characterized oncogenic drivers in a variety of neurogenic and non-neurogenic human neoplasms and are currently the focus of intensive clinical research. Previously, we have described the clinical translation of a highly selective and potent carbon-11-labeled pan-Trk radioligand and the preclinical characterization of the optimized fluorine-18-labeled analogue, [18F]­TRACK, for in vivo Trk positron emission tomography (PET) imaging. We describe herein central nervous system selectivity assessment and first-in-human study of [18F]­TRACK.