Evaluation of radioiodinated (-)-o-iodovesamicol as a radiotracer for mapping the vesicular acetylcholine transporter.
We evaluated the potencies of radioiodinated (-)-o-iodovesamicol [(-)-oIV] as a selective vesicular acetylcholine transporter (VAChT) mapping agent. (-)-[125I]oIV exhibited significant accumulation (about 2.8% of the injected dose) in rat brain. The regional brain distribution of radioactivity was similar for both (-)-[125I]olV and (-)-[3H]vesamicol. The accumulation of (-)-[125I]oIV in the brain was significant reduced by post-administration of unlabeled vesamicol (0.5 /micromol/kg(-1)) and (-)-oIV (0.5 micromol/kg(-1)). On the other hand, the post-administration of sigma ligands hardly affected the accumulation of (-)-[125I]oIV in the brain. These studies showed that (-)-[125I]oIV, as well as [3H] vesamicol, bound to VAChT with high affinity in the rat brain. Furthermore, (-)-[125I]oIV binding in the ipsilateral cortex to the lesion was significantly reduced by 17.0%, compared with that in the contralateral cortex in a unilateral NBM-lesioned rat. These results suggested that radioiodinated (-)-oIV may potentially be useful for the diagnosis of cholinergic neurodegenerative disorders.
Radioisotope Center, School of Medicine, Kanazawa University, Ishikawa, Japan. shiba@med.kanazawa-u.ac.jp
Kazuhiro
K
Shiba
Hirofumi
H
Mori
Norihisa
N
Tonami
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D007051:Ibotenic Acid; D007457:Iodine Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D026901:Membrane Transport Proteins; D008657:Metabolic Clearance Rate; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000378:metabolism*; D009928:Organ Specificity; D010880:Piperidines / Q000737:chemistry / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D007457:Iodine Radioisotopes; D026901:Membrane Transport Proteins; D010880:Piperidines; D019275:Radiopharmaceuticals; C493461:Slc18a3 protein, rat; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins; D007051:Ibotenic Acid; C006189:vesamicol