title: Evaluation of (+)-p-[11C]methylvesamicol for mapping sigma1 receptors: a comparison with [11C]SA4503.
abstract: Vesamicol is a leading compound for positron emission tomography (PET) and single photon emission computed tomography (SPECT) tracers for mapping the vesicular acetylcholine transporter (VAChT). Recently, we found that (+)-p-methylvesamicol ((+)-PMV) has low affinity for VAChT (K(i)=199 nM), but has moderate to high affinity for sigma receptors: K(i)=3.0 nM for sigma1 and K(i)=40.7 nM for sigma2, and that sigma1-selective SA4503 (K(i)=4.4 nM for sigma1 and K(i)=242 nM for sigma2) has moderate affinity for VAChT (K(i)=50.2 nM). In the present study, we examined the potential of (+)-[11C]PMV as a PET radioligand for mapping sigma1 receptors as compared with [11C]SA4503. In rat brain, similar regional distribution patterns of (+)-[11C]PMV and [11C]SA4503 were shown by tissue dissection and by ex vivo autoradiography. Blocking experiments using (+/-)-PMV, (-)-vesamicol, SA4503, haloperidol and (+/-)-pentazocine showed that the two tracers specifically bound to sigma1 receptors, and that [11C]SA4503 exhibited greater specific binding than (+)-[11C]PMV. No sign of VAChT-specific binding by [11C]SA4503 was observed in the striatum, which is rich in VAChT sites. In conclusion, (+)-[11C]PMV specifically bound to sigma1 receptors in the brain, but to a lesser extent than [11C]SA4503, suggesting that (+)-[11C]PMV is a less preferable PET ligand than [11C]SA4503. On the other hand, the moderate affinity of [11C]SA4503 for VAChT is negligible in vivo.
authors.affiliation: Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0022, Japan. ishiwata@pet.tmig.or.jp
authors.forename: Kiichi
authors.initials: K
authors.lastname: Ishiwata
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kawamura
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Yajima
authors.lastname: QingGeLeTu
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Mori
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Shiba
mesh_terms: D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D008657:Metabolic Clearance Rate; D010879:Piperazines / Q000493:pharmacokinetics*; D010880:Piperidines / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D017480:Receptors, sigma / Q000819:agonists / Q000378:metabolism*; D014018:Tissue Distribution; D000097605:Sigma-1 Receptor
chemical_list: D002250:Carbon Radioisotopes; D010879:Piperazines; D010880:Piperidines; D019275:Radiopharmaceuticals; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor; C006189:vesamicol; C101789:SA 4503