Synthesis and evaluation of (11)C-labeled (S)-N-[[1-(2-phenylethyl) pyrrolidin-2-yl]methyl]-3-methylthiobenzamide as a PET 5-HT(1A) receptor ligand.
We prepared 5-HT(1A) receptor ligands (S)-N-[[1-(2-phenylethyl)pyrrolidin-2-yl]methyl]-3-[11C]methylthiobenzamide ([11C](S)-PPMMB) (Ki = 4.3 nM) and the less active [(11)C](R)-PPMMB (Ki = 160 nM) by reduction of the disulfide dimer and subsequent [(11)C]methylation of demethyl (S)- and (R)-PPMMB, respectively. Both radioligands showed similar brain distribution in mice with relatively higher affinity for the hippocampus being rich in 5-HT(1A) receptors than for other brain regions. Uptake of [(11)C](S)-PPMMB was not reduced by carrier-loading nor by pretreatment with 5-HT(1A) receptor ligands. [(11)C](S)-PPMMB is therefore not a suitable radioligand for mapping 5-HT(1A) receptors using positron emission tomography.
Fujio
Masakazu
M
Mitsubishi Pharma Corporation, 7-25, Koyata 3-chome, Iruma, Saitama, 358-0026, Japan.
Nagata
Shinji
S
Kawamura
Kazunori
K
Sugiyama
Naoki
N
Tanaka
Hiroshi
H
Uno
Kimiichi
K
Ishiwata
Kiichi
K
D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008297:Male; D051379:Mice; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013440:Sulfides / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
D001549:Benzamides; C471421:N-((1-(2-phenylethyl)pyrrolidin-2-yl)methyl)-3-methylthiobenzamide; D019275:Radiopharmaceuticals; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D013440:Sulfides