The potential of (-)-o-[11C]methylvesamicol for diagnosing cholinergic deficit dementia.
(-)-o-Methylvesamicol ((-)-OMV) exhibited in vitro a high affinity for a vesicular acetylcholine transporter (VAChT) (Ki, 6.7 nM), and (-)-o-[(11)C]methylvesamicol [(-)-[(11)C]OMV] exhibited appropriate kinetics and bound mainly to VAChTs in the rat brain. In this study, the in vivo distribution and kinetics of (-)-[(11)C]OMV were evaluated in comparison with [(11)C]SA4503 in disability model monkeys produced by selectively destroying the p75NTR-positive cells in the right hemisphere of the brain using positron emission tomography. Time-activity curves of (-)-[(11)C]OMV showed peaks within 20 min in regions rich in acetylcholine transporters (AchT). (-)-[(11)C]OMV binding in the ipsilateral cortex to the lesion was significantly reduced by 22.0% +/- 6.7% when compared with that in the contralateral region. The decrease (19.3% +/- 2.2%) in (-)-[(11)C]OMV binding in the ipsilateral temporal cortex to the lesion was greater than that (7.4% +/- 4.6%) of [(11)C]SA4503. These results suggested that (-)-[(11)C]OMV may be useful in the study of dementia characterized by degeneration of the cholinergic neurotransmitter system.
Shiba
Kazuhiro
K
Advanced Science Research Center, Kanazawa University, Kanazawa, Ishikawa, Japan. shiba@med.kanazawa-u.ac.jp
Nishiyama
Shingo
S
Tsukada
Hideo
H
Ishiwata
Kiichi
K
Kawamura
Kazunori
K
Ogawa
Kazuma
K
Mori
Hirofumi
H
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D003704:Dementia / Q000000981:diagnostic imaging* / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D010880:Piperidines / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D050494:Vesicular Acetylcholine Transport Proteins / Q000378:metabolism*
D002250:Carbon Radioisotopes; D010880:Piperidines; D019275:Radiopharmaceuticals; D050494:Vesicular Acetylcholine Transport Proteins; C006189:vesamicol; D000109:Acetylcholine