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PET Imaging of ABC Transporters at the Blood-Brain Barrier

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PET and SPECT of Neurobiological Systems

Abstract

The function of ATP-binding cassette (ABC) transporters at the blood-brain barrier (BBB) is to protect the brain from toxic compounds. Additionally, they play a crucial role in the onset and progression of several central nervous system (CNS) diseases as well as in drug resistance. Many compounds were identified as substrates, inhibitors, inducers, or activators for ABC transporters, causing important drug-drug interactions. PET imaging represents an excellent tool for assessing the function and expression of ABC transporters. Over the last years, many PET tracers with different characteristics have been developed, mainly for measuring P-glycoprotein (P-gp) function at the BBB. Although (R)-[11C]verapamil or [11C]N-desmethyl-loperamide are considered as the “gold standard” P-gp tracers, they have several drawbacks such as its high affinity to P-gp which limits its use for assessing P-gp increased function. Therefore, PET tracers with lower affinity to the transporter have been developed and studied in different species. The assessment of ABC transporters by PET imaging can provide new insight into the physiology and pathophysiology of different CNS diseases and may open new avenues for therapies. Moreover, PET can be used for screening the affinity of new entities toward various ABC transporters and thus enhance the development of CNS drugs.

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Authors and Affiliations

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

    Lara García-Varela, Pascalle Mossel, Philip Elsinga, Aren van Waarde & Gert Luurtsema

  2. Pharmacy Department, Hadassah Medical Center, Ein Kerem Campus, Jerusalem, Israel

    Marcel Benadiba

  3. Pharmtrace klinische Entwicklung GmbH, Berlin, Germany

    Heli Savolainen

  4. Department of Pharmacy, University of Bari Aldo Moro, Bari, Italy

    Nicola A. Colabufo

  5. Biofordrug, Spin-off Università degli Studi di Bari “A. Moro”, Bari, Italy

    Nicola A. Colabufo

  6. Department of Radiology and Nuclear Medicine, Amsterdam UMC, VU Medical Center, Amsterdam, The Netherlands

    Albert D. Windhorst

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  1. Lara García-Varela
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  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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García-Varela, L. et al. (2021). PET Imaging of ABC Transporters at the Blood-Brain Barrier. 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_22

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  • DOI: https://doi.org/10.1007/978-3-030-53176-8_22

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-53175-1

  • Online ISBN: 978-3-030-53176-8

  • eBook Packages: MedicineMedicine (R0)

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