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Synthesis and labelling with 18F of an MK 801 analogue: [18F]5-(β-fluoruethyl)-10,11-dihydro-5H-dibenzocycloheptene-5,10-imine

✍ Scribed by A. Denis; C. Crouzel


Publisher
John Wiley and Sons
Year
1989
Tongue
French
Weight
230 KB
Volume
27
Category
Article
ISSN
0022-2135

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✦ Synopsis


The 5-(P--fluoro)ethyl analogue 1 of MK 801 2 was synthesized and labelled with 18F in order to visualize the NMDA receptors by positron emission tomography. A tosyloxy precursor 3 was synthesized in 8 steps from dibromodibenzosuberone; the nucleophilic substitution of the tosyl group of 2 by the K FIKrytofix 2,2,2 complex in CH3CN gave [18FJ 1 in 25% radiochemical yield with a specific activity of 40 GBq/pmol (1 Ci/pmol).

18

The major excitatory amino acids in mammalian brain CNS, L.glutamate and L. aspartate, have a neurotoxic activity mediated through excitatory synaptic receptors such as N-Methyl-D-Aspartate ( NMDA ) receptor subtype.

These excitotoxic amino acids have been implicated in several brain damages associated with epilepsy, anoxia-ischemia and hypoglycemia (1). MK 801

1 is a potent and non-competitive antagonist of NMDA (2).

MK 801 was shown, in animal models, to protect against hypoxic-ischemic damage and NMDA neurotoxicity * author to whom reprint requests should be adressed.