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ACS Chem Neurosci. 2019 Jun 19;10(6):2697-2702. doi: 10.1021/acschemneuro.9b00144. Epub 2019 Apr 29.

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

Author information

1
Department of Oncology , University of Alberta , Edmonton , Alberta T6G 2R3 , Canada.
2
Department of Nuclear Medicine , Ludwig-Maximilians-University of Munich , Munich 81377 , Germany.
3
McConnel Brain Imaging Centre, Montreal Neurological Institute , McGill University , 3801 University Street , Montreal , Quebec H3A 2B4 , Canada.
4
Jewish General Hospital , Lady Davis Institute , Montreal , Quebec HT3 1E2 , Canada.
5
Translational Neuroimaging Laboratory, McGill Centre for Studies in Aging , Douglas Mental Health University Institute , Montreal , Quebec H4H 1R3 , Canada.
6
Division of Nuclear Medicine, Department of Radiology , The University of Michigan Medical School , Ann Arbor , Michigan 48109 , United States.
7
Program in Neurosciences and Mental Health , Hospital for Sick Children , Toronto , Ontario M5G 0A4 , Canada.
8
Biomedical Chemistry, Department of Clinical Radiology and Nuclear Medicine , Medical Faculty Mannheim of Heidelberg University , 68167 Mannheim , Germany.
9
Molecular Imaging and Radiochemistry, Department of Clinical Radiology and Nuclear Medicine , Medical Faculty Mannheim of Heidelberg University , Mannheim 68167 , Germany.

Abstract

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.

KEYWORDS:

PET; Trk; Tropomyosin receptor kinase; copper-mediated radiofluorination; fluorine-18; kinase inhibitor; neuroimaging; positron emission tomography

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