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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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Received: 24 November 2011; in revised form: 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 which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

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.

AMA Style

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(2):169-188.

Chicago/Turabian Style

Funke, Uta; Deuther-Conrad, Winnie; Schwan, Gregor; Maisonial, Aurélie; Scheunemann, Matthias; Fischer, Steffen; Hiller, Achim; Briel, Detlef; Brust, Peter. 2012. "Radiosynthesis and Radiotracer Properties of a 7-(2-[18F]Fluoroethoxy)-6-methoxypyrrolidinylquinazoline for Imaging of Phosphodiesterase 10A with PET." Pharmaceuticals 5, no. 2: 169-188.


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