Radiosynthesis and Radiotracer Properties of a 7-(2-[18F]Fluoroethoxy)-6-methoxypyrrolidinylquinazoline for Imaging of Phosphodiesterase 10A with PET
| Autor: | Maisonial-Besset, Aurélie, Funke, Uta, Deuther-Conrad, Winnie, Schwan, Gregor, Maisonial, Aurélie, Scheunemann, Matthias, Fischer, Steffen, Hiller, Achim, Briel, Detlef, Brust, Peter |
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| Přispěvatelé: | Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Institute of Radiopharmacy, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Synthèse et étude de systèmes à intêret biologique (SEESIB), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Pathology
medicine.medical_specialty Biodistribution positron emission tomography lcsh:Medicine lcsh:RS1-441 Pharmaceutical Science PDE10A quinazoline fluorine-18 PET Article lcsh:Pharmacy and materia medica 03 medical and health sciences 0302 clinical medicine In vivo Drug Discovery Radioligand Medicine [CHIM]Chemical Sciences ComputingMilieux_MISCELLANEOUS 030304 developmental biology 0303 health sciences business.industry [CHIM.ORGA]Chemical Sciences/Organic chemistry lcsh:R Radiosynthesis Phosphodiesterase Ligand (biochemistry) Intracellular signal transduction Biochemistry Molecular Medicine business [CHIM.RADIO]Chemical Sciences/Radiochemistry 030217 neurology & neurosurgery |
| Zdroj: | Pharmaceuticals Policy and Law Pharmaceuticals Policy and Law, IOS Press, 2012, 5 (12), pp.169-188. ⟨10.3390/ph5020169⟩ Pharmaceuticals Pharmaceuticals, Vol 5, Iss 2, Pp 169-188 (2012) Pharmaceuticals; Volume 5; Issue 2; Pages: 169-188 Pharmaceuticals Policy and Law, 2012, 5 (12), pp.169-188. ⟨10.3390/ph5020169⟩ |
| ISSN: | 1389-2827 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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