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Pharmaceuticals 2012, 5(2), 169-188; doi:10.3390/ph5020169
Article

Radiosynthesis and Radiotracer Properties of a 7-(2-[18F]Fluoroethoxy)-6-methoxypyrrolidinylquinazoline for Imaging of Phosphodiesterase 10A with PET

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1 Institute of Radiopharmacy, Research Site Leipzig, Helmholtz-Zentrum Dresden-Rossendorf, Permoserstraße 15, Leipzig 04318, Germany 2 Institute of Pharmacy, Universität Leipzig, Brüderstraße 34, Leipzig 04103, Germany
* Author to whom correspondence should be addressed.
Received: 24 November 2011 / Revised: 18 January 2012 / Accepted: 19 January 2012 / Published: 6 February 2012
(This article belongs to the Special Issue Radiochemistry)
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Abstract

Phosphodiesterase 10A (PDE10A) is a key enzyme of intracellular signal transduction which is involved in the regulation of neurotransmission. The molecular imaging of PDE10A by PET is expected to allow a better understanding of physiological and pathological processes related to PDE10A expression and function in the brain. The aim of this study was to develop a new 18F-labeled PDE10A ligand based on a 6,7-dimethoxy-4-pyrrolidinylquinazoline and to evaluate its properties in biodistribution studies. Nucleophilic substitution of the 7-tosyloxy-analogue led to the 7-[18F]fluoroethoxy-derivative [18F]IV with radiochemical yields of 25% ± 9% (n = 9), high radiochemical purity of ≥99% and specific activities of 110–1,100 GBq/μmol. [18F]IV showed moderate PDE10A affinity (KD,PDE10A = 14 nM) and high metabolic stability in the brain of female CD-1 mice, wherein the radioligand entered rapidly with a peak uptake of 2.3% ID/g in striatum at 5 min p.i. However, ex vivo autoradiographic and in vivo blocking studies revealed no target specific accumulation and demonstrated [18F]IV to be inapplicable for imaging PDE10A with PET.
Keywords: PDE10A; quinazoline; fluorine-18; positron emission tomography; PET PDE10A; quinazoline; fluorine-18; positron emission tomography; PET
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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Funke, U.; Deuther-Conrad, W.; Schwan, G.; Maisonial, A.; Scheunemann, M.; Fischer, S.; Hiller, A.; Briel, D.; Brust, P. Radiosynthesis and Radiotracer Properties of a 7-(2-[18F]Fluoroethoxy)-6-methoxypyrrolidinylquinazoline for Imaging of Phosphodiesterase 10A with PET. Pharmaceuticals 2012, 5, 169-188.

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