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Transporters as Targets for Drugs pp 155–186Cite as

Molecular Imaging of Transporters with Positron Emission Tomography

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Part of the book series: Topics in Medicinal Chemistry ((TMC,volume 4))

Abstract

Positron emission tomography (PET) visualization of brain components in vivo is a rapidlygrowing field. Molecular imaging with PET is also increasingly used in drug development, especiallyfor the determination of drug receptor interaction for CNS-active drugs. This gives the opportunityto relate clinical efficacy to per cent receptor occupancy of a drug on a certain targetedreceptor and to relate drug pharmacokinetics in plasma to interaction with target protein. In thepresent review we will focus on the study of transporters, such as the monoamine transporters, theP-glycoprotein (Pgp) transporter, the vesicular monoamine transporter type 2, and the glucosetransporter using PET radioligands. Neurotransmitter transporters are presynaptically located andin vivo imaging using PET can therefore be used for the determination of the density of afferent neurons.Several promising PET ligands for the noradrenaline transporter (NET) have been labeled and evaluatedin vivo including in man, but a really useful PET ligand for NET still remains to be identified.The most promising tracer to date is (S,S)-[18F]FMeNER-D2.The in vivo visualization of the dopamine transporter (DAT) may give clues in the evaluation of conditionsrelated to dopamine, such as Parkinson's disease and drug abuse. The first PET radioligands basedon cocaine were not selective, but more recently several selective tracers such as [11C]PE2Ihave been characterized and shown to be suitable as PET radioligands. Although there are a largenumber of serotonin transporter inhibitors used today as SSRIs, it was not until very recently, when[11C]McN5652 was synthesized, that this transporter was studied using PET.New candidates as PET radioligands for the SERT have subsequently been developed and [11C]DASBand [11C]MADAM and their analogues are today the most promising ligands.The existing radioligands for Pgp transporters seem to be suitable tools for the study of both peripheraland central drug–Pgp interactions, although [11C]verapamil and [18F]fluoropaclitaxelare probably restricted to use in studies of the blood–brain barrier. The vesicular monoaminetransporter 2 (VMAT2) is another interesting target for diagnostic imaging and [11C]DTBZis a promising tracer. The noninvasive imaging of transporter density as a function ofdisease progression or availability following interaction with blocking drugs is highlighted, includingthe impact on both development of new therapies and the process of developing new drugs. AlthoughCNS-related work focusing on psychiatric disorders is the main focus of this review, other applicationsof PET ligands, such as diagnosis of cancer, diabetes research, and drug interactions with effluxsystems, are also discussed. The use of PET especially in terms of tracer development is brieflydescribed. Finally, it can be concluded that there is an urgent need for new, selective radioligandsfor the study of the transporter systems in the human brain using PET.

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Authors and Affiliations

  1. Uppsala Imanet AB, GE Healthcare, P.O. Box 967, 75109, Uppsala, Sweden

    Gunnar Antoni & Jens Sörensen

  2. Uppsala Applied Science Lab, GE Healthcare, P.O. Box 967, 75109, Uppsala, Sweden

    Håkan Hall

Authors
  1. Gunnar Antoni
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  2. Jens Sörensen
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  3. Håkan Hall
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Correspondence to Gunnar Antoni .

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Susan Napier Matilda Bingham

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© 2008 Springer-Verlag Berlin Heidelberg

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Antoni, G., Sörensen, J., Hall, H. (2008). Molecular Imaging of Transporters with Positron Emission Tomography. In: Napier, S., Bingham, M. (eds) Transporters as Targets for Drugs. Topics in Medicinal Chemistry, vol 4. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7355_2008_025

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