title: Chemical fate of the nicotinic acetylcholinergic radiotracer [123I]5-IA-85380 in baboon brain and plasma.
abstract: The fate of the nicotinic acetylcholinergic receptor radiotracer [123I]5-IA-85380 ([123I]5-IA) was studied in baboon by analyzing the chemical composition of brain tissue and plasma after intravenous administration of the tracer. Acetonitrile denaturation and high-performance liquid chromatography (HPLC) analysis showed predominantly unchanged (91-98%) parent tracer in all brain tissues examined, compared to significant metabolism (23% parent) in the plasma at 90 min postinjection, and control tissue recovery of 95-98%. [123I]5-IA was distributed to the thalamus with a standardized uptake value of 9.2 (0.04% dose/g) or a concentration 5.8 times higher than that of the cerebellum. The HPLC behavior of a synthesized sample of one hypothesized metabolite, 5-iodo-3-pyridinol (5-IP), was consistent with plasma radiometabolite fraction. Since only parent radiotracer compound was found in brain tissue, these results add confidence that information derived from single photon emission computed tomography images of 123I activity in the brain after [123I]5-IA administration can be interpreted as distribution of an intact radiotracer.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06510, USA. ronald.baldwin@vanderbilt.edu
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Baldwin
authors.forename: Sami S
authors.initials: SS
authors.lastname: Zoghbi
authors.forename: Julie K
authors.initials: JK
authors.lastname: Staley
authors.forename: Eric
authors.initials: E
authors.lastname: Brenner
authors.forename: Mohammed S
authors.initials: MS
authors.lastname: Al-Tikriti
authors.forename: Louis
authors.initials: L
authors.lastname: Amici
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fujita
authors.forename: Robert B
authors.initials: RB
authors.lastname: Innis
authors.forename: Gilles
authors.initials: G
authors.lastname: Tamagnan
mesh_terms: D000818:Animals; D001384:Azetidines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D009928:Organ Specificity; D048530:Papio anubis; D011725:Pyridines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D011978:Receptors, Nicotinic / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: C426745:5-iodo-3-(2-azetidinylmethoxy)pyridine; D001384:Azetidines; D011725:Pyridines; D019275:Radiopharmaceuticals; D011978:Receptors, Nicotinic