High-yield radiosynthesis and preliminary in vivo evaluation of p-[18F]MPPF, a fluoro analog of WAY-100635.

Animals; Brain/metabolism; Cats; Chromatography, High Pressure Liquid; Female; Fluorine Radioisotopes/diagnostic use/pharmacokinetics; Molecular Structure; Piperazines/chemical synthesis/diagnostic use/pharmacokinetics; Pyridines/chemical synthesis/diagnostic use/pharmacokinetics; Quality Control; Radioligand Assay; Radiopharmaceuticals/chemical synthesis/diagnostic use/pharmacokinetics; Serotonin Antagonists/chemical synthesis/diagnostic use/pharmacokinetics; Tomography, Emission-Computed

Abstract :

[en] No-carrier-added 4-[18F]fluoro-N-[2-[1-(2-methoxyphenyl)-1 piperazinyl]ethyl-N-2-pyridinyl-benzamide (p-[18F]MPPF) was synthesized by nucleophilic substitution of the corresponding nitro compound in the presence of Kryptofix 222 and K2CO3 by microwave heating (3 min, 500 W) using a remotely controlled radiosynthesis. Baseline separation of p-[18F]MPPF from the nitro derivative was performed on a semipreparative HPLC C18 column. After Sep-Pak formulation, the radiopharmaceutical was obtained with a radiochemical yield of 25% (EOS) in about 70 min. Specific radioactivity averaged between 1-5 Ci/micromol EOS. Labelling of the ortho and meta derivatives was also attempted. Brain uptake of p-[18F]MPPF was studied with PET on fluothane-anesthetized cats. Following intravenous injection of p-[18F]MPPF, high accumulation of radioactivity was observed in the hippocampus and cerebral cortex. Low levels of radioactivity were observed in cerebellum. At 30 min, the mean hippocampus/cerebellum and cortex/cerebellum ratios were 5 and 3.8, respectively. The accumulation of the tracer was blocked by prior administration of reference WAY-100635, demonstrating the specificity of the ligand.

Research Center/Unit :

GIGA CRC (Cyclotron Research Center) In vivo Imaging-Aging & Memory - ULiège
CERMEP Lyon

Disciplines :

Radiology, nuclear medicine & imaging

Author, co-author :

Le Bars, Didier; Centre d'Exploration et de Recherche Médicales par Émission de Positons - CERMEP (Lyon)

Lemaire, Christian ; Université de Liège - ULiège > Centre de recherches du cyclotron

Ginovart, N.

Plenevaux, Alain ; Université de Liège - ULiège > Centre de recherches du cyclotron

Aerts, Joël ; Université de Liège - ULiège > Centre de recherches du cyclotron

Brihaye, C.

Hassoun, W.

Leviel, V.

Mekhsian, P.

Weissmann, D.

More authors (3 more)

Language :

English

Title :

High-yield radiosynthesis and preliminary in vivo evaluation of p-[18F]MPPF, a fluoro analog of WAY-100635.

Publication date :

1998

Journal title :

Nuclear Medicine and Biology

ISSN :

0969-8051

Publisher :

Pergamon Press, Oxford, United Kingdom

Volume :

Issue :

Pages :

343-50

Peer reviewed :

Peer Reviewed verified by ORBi

Funders :

F.R.S.-FNRS - Fonds de la Recherche Scientifique

Available on ORBi :

since 29 January 2009

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137

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101

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109

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140

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