Evaluation of radioiodinated (-)-o-iodovesamicol as a radiotracer for mapping the vesicular acetylcholine transporter

• Published in: Annals of nuclear medicine Vol. 17; no. 6; pp. 451 - 456
• Main Authors: Shiba, Kazuhiro, Mori, Hirofumi, Tonami, Norihisa
• Format: Journal Article
• Language: English
• Published: Japan Springer Nature B.V 01-09-2003
• Subjects: Accumulation; Acetylcholine; Animals; Brain; Brain - diagnostic imaging; Brain - metabolism; Carrier Proteins - metabolism; Cholinergics; Ibotenic Acid; Iodine isotopes; Iodine Radioisotopes - chemistry; Iodine Radioisotopes - pharmacokinetics; Isotope Labeling - methods; Male; Mapping; Membrane Transport Proteins; Metabolic Clearance Rate; Neurodegenerative diseases; Neurodegenerative Diseases - chemically induced; Neurodegenerative Diseases - diagnostic imaging; Neurodegenerative Diseases - metabolism; Organ Specificity; Piperidines - chemistry; Piperidines - pharmacokinetics; Radioactive tracers; Radioactivity; Radionuclide Imaging; Radiopharmaceuticals - chemical synthesis; Radiopharmaceuticals - pharmacokinetics; Rats; Reproducibility of Results; Sensitivity and Specificity; Tissue Distribution; Vesamicol; Vesicular Acetylcholine Transport Proteins; Vesicular acetylcholine transporter; Vesicular Transport Proteins
• ISSN: 0914-7187; 1864-6433
• DOI: 10.1007/bf03006433

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.