The potential of (-)-o-[11C]methylvesamicol for diagnosing cholinergic deficit dementia.

Abstract

(-)-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.

• Authors: Kazuhiro Shiba, Shingo Nishiyama, Hideo Tsukada, Kiichi Ishiwata, Kazunori Kawamura, Kazuma Ogawa, Hirofumi Mori
• Journal: Synapse (New York, N.Y.) (Synapse) Vol. 63 Issue 2 Pg. 167-71 (Feb 2009) ISSN: 1098-2396 [Electronic] United States
• PMID: 19021207 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: 2008 Wiley-Liss, Inc.

Chemical References

• Carbon Radioisotopes
• Piperidines
• Radiopharmaceuticals
• Vesicular Acetylcholine Transport Proteins
• vesamicol
• Acetylcholine

Topics

• Acetylcholine (metabolism)
• Animals
• Brain (diagnostic imaging, metabolism)
• Carbon Radioisotopes (pharmacokinetics)
• Dementia (diagnostic imaging, metabolism)
• Macaca mulatta
• Male
• Piperidines (pharmacokinetics)
• Positron-Emission Tomography
• Radiopharmaceuticals (pharmacokinetics)
• Vesicular Acetylcholine Transport Proteins (metabolism)