Central Nervous System Agents in Medicinal Chemistry

(Formerly Current Medicinal Chemistry - Central Nervous System Agents)


PET Tracers for Mapping Adenosine Receptors as Probes for Diagnosis of CNS Disorders

Author(s): Kiichi Ishiwata, Yuichi Kimura, Erik F. J. de Vries and Philip H. Elsinga

Affiliation: Positron Medical Center,Tokyo Metropolitan Institute of Gerontology, 1-1, Naka, Itabashi, Tokyo,173-0011, Japan.


Adenosine is an endogenous modulator of several physiological functions in the central nervous system (CNS). The effect is mediated by a receptor family that consists of at least four subtypes: A1, A2A, A2B and A3 receptors. The adenosine receptors play a role in neurological and psychiatric disorders such as Alzheimers disease, Parkinsons disease, epilepsy and schizophrenia. Knowledge on adenosine receptor densities and status are important for understanding the mechanisms underlying the pathogenesis of diseases and for developing new therapeutics. Positron emission tomography (PET) offers a non-invasive tool to investigate these features in vivo, provided that suitable radiopharmaceuticals are available. As a consequence of the development of xanthine-type adenosine receptor antagonists with high affinity and high selectivity, several PET ligands labeled with carbon-11 (half-life of 20.4 min) and fluorine-18 (half-life of 109.8 min) have been proposed for mapping the adenosine A1 and A2A receptors (A1R and A2AR, respectively) and the adenosine uptake site in the CNS since 1995. Later non-xanthine-type antagonists for A2AR were radiolabeled. So far two tracers for A1R, [18F]CPFPX and [11C]MPDX, and a tracer for A2AR, [11C]TMSX (also called [11C]KF18446), have been applied to humans. For the other subtypes and the adenosine uptake site no suitable radioligands have been developed yet. This paper gives an overview of the current status on PET tracers for mapping adenosine receptors and the development of new compounds that may lead to new PET tracers.

Keywords: Adenosine receptor, radiolabeled ligand, positron emission tomography, xanthine

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Article Details

Page: [57 - 77]
Pages: 21
DOI: 10.2174/187152407780059259