2. Academic Validation
  3. Radioligands for Tropomyosin Receptor Kinase (Trk) Positron Emission Tomography Imaging

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

  • Pharmaceuticals (Basel). 2019 Jan 3;12(1):7. doi: 10.3390/ph12010007.
Ralf Schirrmacher 1,  Justin J Bailey 2,  Andrew V Mossine 3,  Peter J H Scott 4 5,  Lena Kaiser 6,  Peter Bartenstein 7,  Simon Lindner 8,  David R Kaplan 9,  Alexey Kostikov 10,  Gert Fricker 11,  Anne Mahringer 12,  Pedro Rosa-Neto 13,  Esther Schirrmacher 14,  Carmen Wängler 15,  Björn Wängler 16,  Alexander Thiel 17 18,  Jean-Paul Soucy 19,  Vadim Bernard-Gauthier 20 21
Affiliations

Affiliations

  • 1 Department of Oncology, Division of Oncological Imaging, University of Alberta, Edmonton, Alberta T6G 2R3, Canada. [email protected].
  • 2 Department of Oncology, Division of Oncological Imaging, University of Alberta, Edmonton, Alberta T6G 2R3, Canada. [email protected].
  • 3 Division of Nuclear Medicine, Department of Radiology, The University of Michigan Medical School, Ann Arbor, MI, 48109, USA. [email protected].
  • 4 Division of Nuclear Medicine, Department of Radiology, The University of Michigan Medical School, Ann Arbor, MI, 48109, USA. [email protected].
  • 5 The Interdepartmental Program in Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109, USA. [email protected].
  • 6 Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Marchioninistrasse 15, Munich 81377, Germany. [email protected].
  • 7 Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Marchioninistrasse 15, Munich 81377, Germany. [email protected].
  • 8 Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Marchioninistrasse 15, Munich 81377, Germany. [email protected].
  • 9 Program in Neurosciences and Mental Health, Hospital for Sick Children and Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada M5G 0A4. [email protected].
  • 10 McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada. [email protected].
  • 11 Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg, Heidelberg 69120, Germany. [email protected].
  • 12 Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg, Heidelberg 69120, Germany. [email protected].
  • 13 Translational Neuroimaging Laboratory, McGill Centre for Studies in Aging, Douglas Mental Health University Institute, Montreal, QC H4H 1R3, Canada. [email protected].
  • 14 Department of Oncology, Division of Oncological Imaging, University of Alberta, Edmonton, Alberta T6G 2R3, Canada. [email protected].
  • 15 Biomedical Chemistry, Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim of Heidelberg University, 68167 Mannheim, Germany. [email protected].
  • 16 Molecular Imaging and Radiochemistry, Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim of Heidelberg University, Theodor-Kutzer-Ufer 1-3, Mannheim 68167, Germany. [email protected].
  • 17 McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada. [email protected].
  • 18 Jewish General Hospital, Lady Davis Institute, Montreal, QC HT3 1E2, Canada. [email protected].
  • 19 McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada. [email protected].
  • 20 Azrieli Centre for Neuro-Radiochemistry, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON M5T 1L8, Canada. [email protected].
  • 21 Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada. [email protected].
PMID: 30609832 DOI: 10.3390/ph12010007
Abstract

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.

Keywords

neurodegeneration; oncogenic fusions; positron emission tomography; tropomyosin receptor kinase.

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