NMDA receptor channels: Labeling of MK-801 with iodine-125 and fluorine-18

• Published in: International journal of radiation applications and instrumentation. Part A, Applied radiation and isotopes Applied radiation and isotopes, 1988, Vol.39 (12), p.1219-1225
• Main Authors: Wieland, D.M., Kilbourn, M.R., Yang, D.J., Laborde, E., Gildersleeve, D.L., van Dort, M.E., Pirat, J-L., Ciliax, B.J., Young, A.B.
• Format: Article
• Language: English
• Subjects: Animals; Anticonvulsants - chemical synthesis; Anticonvulsants - metabolism; Aspartic Acid - analogs & derivatives; Aspartic Acid - metabolism; Brain - metabolism; Chemical Phenomena; Chemistry; Dibenzocycloheptenes - chemical synthesis; Dibenzocycloheptenes - metabolism; Dizocilpine Maleate; Fluorine Radioisotopes; Iodine Radioisotopes; Male; N-Methylaspartate; Rats; Rats, Inbred Strains; Receptors, N-Methyl-D-Aspartate; Receptors, Neurotransmitter - metabolism
• ISSN: 0883-2889
• DOI: 10.1016/0883-2889(88)90103-7

Methods for labeling the glutamate channel blocking agent MK-801 with iodine-125 ( 125I) and fluorine-18 ( 18F) are described. Radioiodine was incorporated in the 1- or 3-positions of the aromatic ring of (±)MK-801 by solid-state halogen exchange techniques. Attachment of the [ 18F]fluoromethyl group to the bridgehead methyl position was achieved by reaction of [ 18F]fluoride with the triflamide alcohol 8 or the novel cyclic sulfamate 9 recently reported by Merck chemists. Radiochemical yields of (±)13-[ 18 F]- fluoromethyl- MK-801 were >72%, EOB; radiochemical purity >99%. In competitive binding studies using rat brain homogenates, (±)3-bromo-MK-801 showed greater affinity than (±)MK-801 for the glutamate-linked channel. The experimental log P (2.1 ± 0.1) of MK-801 is optimal for transit of the blood-brain barrier. These preliminary findings support further testing of 3-[ 123I]iodo-MK-801 and (±)13-[ 18 F] fluoromethyl- MK-801 as possible agents for in vivo mapping of the glutamate receptor complex.