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Preclinical Testing of Novel Radiotracers for Positron Emission Tomography (PET)

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Quality in Nuclear Medicine

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Abstract

Preclinical tests of novel radiotracers in experimental animals are required to move tracer candidates from the stage of in vitro testing to the stage of toxicity testing and finally studies in human volunteers. Such preclinical tests are aimed at demonstrating: (1) specific in vivo interaction of the tracer with its target, (2) adequate kinetics and metabolic stability of the tracer after it has been injected into living mammals, and (3) sensitivity of tracer uptake to changes of target expression. Possible strategies to reach these aims are discussed, including specific animal models which are used in our institution. These include pharmacological treatment of healthy animals, target gene knockout, tumor growth, brain lesions resulting in loss of myelin, viral infection, sterile inflammation, and xenografting of inflammatory cells.

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Disclaimer

The procedures described above constitute the general approach for validation of a novel radiotracer. However, the milestones on the way should not be interpreted as absolute go/no-go moments. If a tracer fails in one test but passes all others, and if the point of failure concerns an issue which could be present in rodents but be absent in humans (e.g., rapid metabolism), a limited pilot study in primates can still be carried out in order to avoid the premature discarding of a valuable radiopharmaceutical. Such a decision may particularly be made if no other tracers for the target are available.

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Authors and Affiliations

  1. Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Hanzeplein 1, Groningen, 9713 GZ, The Netherlands

    Aren van Waarde, Jürgen W. A. Sijbesma, Janine Doorduin, Philip H. Elsinga & Erik F. J. de Vries

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  1. Aren van Waarde
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  2. Jürgen W. A. Sijbesma
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  3. Janine Doorduin
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  4. Philip H. Elsinga
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  5. Erik F. J. de Vries
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Correspondence to Aren van Waarde .

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Editors and Affiliations

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

    Andor W.J.M. Glaudemans

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

    Jitze Medema

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

    Annie K. van Zanten

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

    Rudi A.J.O. Dierckx

  5. Dutch Institute for Healthcare Improvement, Utrecht, The Netherlands

    C.T.B. (Kees) Ahaus

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van Waarde, A., Sijbesma, J.W.A., Doorduin, J., Elsinga, P.H., de Vries, E.F.J. (2017). Preclinical Testing of Novel Radiotracers for Positron Emission Tomography (PET). In: Glaudemans, A., Medema, J., van Zanten, A., Dierckx, R., Ahaus, C. (eds) Quality in Nuclear Medicine. Springer, Cham. https://doi.org/10.1007/978-3-319-33531-5_17

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