High-yield radiosynthesis and preliminary in vivo evaluation of p-[18F]MPPF, a fluoro analog of WAY-100635.
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.
Le Bars
D
D
CERMEP, Lyon, France. lebars@univ-lyon1.fr
Lemaire
C
C
Ginovart
N
N
Plenevaux
A
A
Aerts
J
J
Brihaye
C
C
Hassoun
W
W
Leviel
V
V
Mekhsian
P
P
Weissmann
D
D
Pujol
J F
JF
Luxen
A
A
Comar
D
D
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002415:Cats; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D011725:Pyridines / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D011786:Quality Control; D011869:Radioligand Assay; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D014055:Tomography, Emission-Computed
C114151:4-fluoro-N-(2-(1-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-2-pyridinylbenzamide; D005462:Fluorine Radioisotopes; D010879:Piperazines; D011725:Pyridines; D019275:Radiopharmaceuticals; D012702:Serotonin Antagonists; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide