Radioligands for Tropomyosin Receptor Kinase (Trk) Positron Emission Tomography Imaging.

TitleRadioligands for Tropomyosin Receptor Kinase (Trk) Positron Emission Tomography Imaging.
Publication TypeJournal Article
Year of Publication2019
AuthorsSchirrmacher R, Bailey JJ, Mossine AV, Scott PJH, Kaiser L, Bartenstein P, Lindner S, Kaplan DR, Kostikov A, Fricker G, Mahringer A, Rosa-Neto P, Schirrmacher E, Wängler C, Wängler B, Thiel A, Soucy J-P, Bernard-Gauthier V
JournalPharmaceuticals (Basel)
Date Published2019 Jan 03

The tropomyosin receptor kinases family (TrkA, TrkB, and TrkC) supports neuronal growth, survival, and differentiation during development, adult life, and aging. TrkA/B/C downregulation is a prominent hallmark of various neurological disorders including Alzheimer's disease (AD). Abnormally expressed or overexpressed full-length or oncogenic fusion TrkA/B/C proteins were shown to drive tumorigenesis in a variety of neurogenic and non-neurogenic human cancers and are currently the focus of intensive clinical research. Neurologic and oncologic studies of the spatiotemporal alterations in TrkA/B/C expression and density and the determination of target engagement of emerging antineoplastic clinical inhibitors in normal and diseased tissue are crucially needed but have remained largely unexplored due to the lack of suitable non-invasive probes. Here, we review the recent development of carbon-11- and fluorine-18-labeled positron emission tomography (PET) radioligands based on specifically designed small molecule kinase catalytic domain-binding inhibitors of TrkA/B/C. Basic developments in medicinal chemistry, radiolabeling and translational PET imaging in multiple species including humans are highlighted.

Alternate JournalPharmaceuticals (Basel)
PubMed ID30609832
Grant List21007 / / Cancer Research Society and C17 Council /
RR161057 / / Weston Brain Institute /
327872 / / Natural Sciences and Engineering Research Council of Canada /
DE-SC0012484 / / U.S. Department of Energy /