Synthesis of (S)-N-[methyl-11C]nicotine and its regional distribution in the mouse brain: a potential tracer for visualization of brain nicotinic receptors by positron emission tomography.
A nicotine agonist, 11C-labeled (S)-nicotine, was synthesized by N-methylation of (S)-nornicotine with [11C]-methyl iodide in dimethylformamide-dimethylsulfoxide in order to study nicotinic receptors in the human brain by positron emission tomography. The radiochemical yield of this N-methylation reaction was more than 90% within 5 min. After purification by high performance liquid chromatography the radiochemical purity of the product was more than 99% and the specific radioactivity was 7.4-11.1 GBq/mumol. The regional distribution of (S)-[11C]nicotine in the mouse brain after intravenous injection was compared with that of (R)-[11C]nicotine. After injection of (S)-[11C]nicotine, the regional uptake of radioactivity was in the following order: cortex greater than thalamu approximately hippocampus greater than striatum greater than hypothalamus greater than cerebellum. Moreover, (S)-[11C]nicotine was displaced from the brain by unlabeled (S)-nicotine, but unlabeled (R)-nicotine caused no change in uptake. In contrast, (R)-[11C]nicotine showed a lower brain uptake and lesser regional differences in radioactivity.
Saji
H
H
Department of Radiopharmaceutical Chemistry, Kyoto University, Japan.
Magata
Y
Y
Yamada
Y
Y
Tajima
K
K
Yonekura
Y
Y
Konishi
J
J
Ohmomo
Y
Y
Yokoyama
A
A
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D007553:Isotope Labeling; D008297:Male; D008745:Methylation; D051379:Mice; D009538:Nicotine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000032:analysis / Q000378:metabolism*; D013237:Stereoisomerism; D014055:Tomography, Emission-Computed
D011978:Receptors, Nicotinic; D009538:Nicotine; C005311:nornicotine