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PET Tracers for Imaging of the Dopaminergic System

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The dopaminergic system plays a major role in neurological and psychiatric disorders such as Parkinson's disease, Huntington's disease, tardive dyskinea and schizophrenia. Knowledge on altered dopamine synthesis, receptor densities and status are important for understanding the mechanisms underlying the pathogenesis and therapy of diseases. PET provides a non-invasive tool to investigate these features in vivo, provided the availability of suitable radiopharmaceuticals.

To investigate presynaptic function, PET-tracers have been developed to measure dopamine synthesis and transport. For the former the most commonly used tracers are 6-[18F]FDOPA and 6-[18F]FMT, whereas for the latter several 11C/18F-labeled tropane analogues are being clinically used. Postsynaptically, dopamine exerts actions through several subtypes of the dopamine receptor. The dopamine receptor family consists of 5 subtypes D1-D5. In order to investigate the role of each receptor subtype, selective and high-affinity PETradioligands are required. For the dopamine D1-subtype the most commonly used ligand is [11C]SCH 23390 or [11C]NNC 112, whereas for the D2/D3-subtype [11C]raclopride is a common tracer. [18 F]Fallypride is a suitable PET-tracer for the investigation of extrapyramidal D2-receptors. For the other subtypes no suitable radioligands have been developed yet.

This paper gives an overview of the current status on dopamine PET-tracers and the development of new lead compounds as potential PET-tracers by medicinal chemistry.

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Keywords: Dopamine synthesis; dopamine receptor; dopamine transporter; positron emission tomography

Document Type: Research Article

Affiliations: University Medical Center Groningen, P.O. Box 30001, 9700 RB Groningen, The Netherlands.

Publication date: 2006-08-01

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