Animals; Chromatography, High Pressure Liquid; Fluorine Radioisotopes; Mice; Molecular Structure; Tissue Distribution
Abstract :
[en] No-carrier-added DL-alpha-methyl-beta-4-[18F]fluorophenyl-N-methyl-N-propynylethylamin e (DL-4-[18F]fluorodeprenyl) was synthesized via the following 3-step procedure: (1) nucleophilic aromatic substitution by [18F]fluoride on 4-nitrobenzaldehyde to produce 4-[18F]fluorobenzaldehyde (yield 65%); (2) the reaction of 4-[18F]fluorobenzaldehyde with (1-chloro-1-(trimethylsilyl)ethyl)lithium followed by hydrolysis to give 4-[18F]fluorophenylacetone (yield 50%); and (3) reductive alkylation of 4-[18F]fluorophenylacetone with N-methyl-propynylamine in the presence of NaBH3CN (yield 35%) followed by HPLC purification to give a racemic mixture of 4-[18F]fluorodeprenyl. The overall yield was 11% (EOB corrected), the synthesis time was 90 min and the specific activity greater than 0.57 Ci/mumol (end of synthesis). This synthesis approach, the conversion of an aromatic aldehyde to a homologous methyl ketone, extends the flexibility of the nucleophilic aromatic substitution reaction by applying it to the synthesis of radiotracers which do not bear electron-withdrawing activating groups on the aromatic ring. The tissue distribution of DL-4-[18F]fluorodeprenyl in mice at 1, 10 and 60 min was also measured and showed that metabolic defluorination was not significant. Clearance of radioactivity from brain after injection of DL-4-[18F]fluorodeprenyl was more rapid than that previously observed for [11C]L-deprenyl.
Research Center/Unit :
GIGA CRC (Cyclotron Research Center) In vivo Imaging-Aging & Memory - ULiège Brookhaven National Laboratory NY USA
Disciplines :
Chemistry
Author, co-author :
Plenevaux, Alain ; Université de Liège - ULiège > Centre de recherches du cyclotron
Fowler, Joanna S.
Dewey, Stephen L.
Wolf, Alfred P.
Guillaume, Marcel
Language :
English
Title :
The synthesis of no-carrier-added DL-4-[18F]fluorodeprenyl via the nucleophilic aromatic substitution reaction.
Publication date :
1991
Journal title :
International Journal of Radiation Applications and Instrumentation. Part A, Applied Radiation and Isotopes
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