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Toward Imaging Tropomyosin Receptor Kinase (Trk) with Positron Emission Tomography

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PET and SPECT of Neurobiological Systems

Abstract

The three tropomyosin receptor kinases (TrkA, B, and C) fulfill important roles within the central nervous system facilitating neuronal growth, neuronal survival, and neuronal differentiation during cell development at all ages of neuronal development. The downregulation of TrkA, B, and C has been identified as an important hallmark of a plethora of neurological diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). In oncology, Trks have been recognized as tumorigenic drivers. Full-length Trk as well as fusion proteins composed of the kinase portion of the full-length receptor and various other cancer-related proteins has been reported, and the targeting of these receptors for a contingent Trk-based therapy has recently caught momentum in the wake of precision medicine evolvement. Both in neurology and oncology, the spatiotemporal changes in Trk expression can only be reviewed via destructive and invasive methods such as taking a tumor biopsy. The quantification of Trk density in neurodegeneration (e.g., AD and PD) as well as cancer treatment, where therapeutic Trk target engagement of antineoplastic Trk inhibitors with Trk fusion proteins is the site of therapeutic action, has triggered the need for a noninvasive methodology to quantify Trk in vivo in these Trk-altering conditions. Positron emission tomography (PET), a noninvasive imaging methodology, relying on the highly sensitive detection of radiation, has the potential to take advantage of radioactively labeled probes binding to the kinase domain of Trk to not only reveal the location of Trk but allow for the quantification of receptor density. This article covers the most recent developments in Trk tracer evolution for PET imaging and their first human in vivo application.

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Author information

Authors and Affiliations

  1. Division of Oncological Imaging, Department of Oncology, University of Alberta, Edmonton, AB, Canada

    Ralf Schirrmacher, Carolin Jaworski & Justin Bailey

  2. Azrieli Centre for Neuro-Radiochemistry, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada

    Vadim Bernard-Gauthier

  3. Biomedical Chemistry, Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim of Heidelberg University, Mannheim, Germany

    Carmen Wängler

  4. Molecular Imaging and Radiochemistry, Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim of Heidelberg University, Mannheim, Germany

    Björn Wängler

Authors
  1. Ralf Schirrmacher
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  2. Vadim Bernard-Gauthier
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  3. Carolin Jaworski
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  4. Carmen Wängler
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  5. Björn Wängler
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  6. Justin Bailey
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Corresponding author

Correspondence to Ralf Schirrmacher .

Editor information

Editors and Affiliations

  1. Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands

    Rudi A.J.O. Dierckx

  2. Faculty of Electrical Engineering, Medical Engineering and Computer Science, Offenburg University, Offenburg, Germany

    Andreas Otte

  3. Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands

    Erik F.J. de Vries

  4. Nuclear Medicine and Molecular Imaging, University Medical Center, Groningen, The Netherlands

    Aren van Waarde

  5. Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers location VUmc, Amsterdam, The Netherlands

    Adriaan A. Lammertsma

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Schirrmacher, R., Bernard-Gauthier, V., Jaworski, C., Wängler, C., Wängler, B., Bailey, J. (2021). Toward Imaging Tropomyosin Receptor Kinase (Trk) with Positron Emission Tomography. In: Dierckx, R.A., Otte, A., de Vries, E.F., van Waarde, A., Lammertsma, A.A. (eds) PET and SPECT of Neurobiological Systems. Springer, Cham. https://doi.org/10.1007/978-3-030-53176-8_31

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  • DOI: https://doi.org/10.1007/978-3-030-53176-8_31

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