title: Synthesis of the 123I- and 125I-labeled cholinergic nerve marker (-)-5-iodobenzovesamicol.
abstract: The highly toxic curraremimetic and cholinergic neuron marker (-)-5-iodobenzovesamicol (IBVM) has been labeled with iodine-125 and iodine-123. [125I]IBVM, suitable for animal distribution and ex vivo autoradiographic studies, was synthesized by solid-state exchange; isolated yields were 65-89% with specific activities in the range of 130-200 Ci/mmol. The synthesis of no-carrier-added (-)-5-[125I]IBVM from the corresponding chiral (-)-5-(tri-n-butyltin) derivative using Na125I was evaluated using the oxidants H2O2, peracetic acid and chloramine-T. Both peracetic acid and chloramine-T gave good yields (70-95%). However, when Na123I was utilized, acceptable yields of [123I]IBVM were obtained only with chloramine-T. Use of the latter oxidant did produce 5-chlorobenzovesamicol which was eliminated during HPLC purification. After optimization of the reaction parameters, [123I]IBVM in batch sizes of 10-27 mCi, is routinely obtained with a specific activity of 30-70,000 Ci/mmol, radiochemical purity (> 97%) and chiral purity (> 98%). Isolated radiochemical yields have averaged 71% (N = 40). Distribution analyses of [125I]IBVM and [123I]IBVM in mice 4 h following intravenous administration show essentially equivalent concentrations of the two tracers in the four brain regions sampled. The exceptionally high specific activity of [123I]IBVM has made possible the evaluation of this radiotracer in humans.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor 48109-0552.
authors.forename: M E
authors.initials: ME
authors.lastname: Van Dort
authors.forename: Y W
authors.initials: YW
authors.lastname: Jung
authors.forename: D L
authors.initials: DL
authors.lastname: Gildersleeve
authors.forename: C A
authors.initials: CA
authors.lastname: Hagen
authors.forename: D E
authors.initials: DE
authors.lastname: Kuhl
authors.forename: D M
authors.initials: DM
authors.lastname: Wieland
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002700:Chloramines / Q000737:chemistry; D002799:Cholinergic Fibers / Q000378:metabolism*; D005260:Female; D006861:Hydrogen Peroxide / Q000737:chemistry; D007202:Indicators and Reagents / Q000737:chemistry; D007457:Iodine Radioisotopes / Q000737:chemistry*; D007553:Isotope Labeling / Q000379:methods; D051379:Mice; D008815:Mice, Inbred Strains; D010463:Peracetic Acid / Q000737:chemistry; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D010880:Piperidines; D013237:Stereoisomerism; D013764:Tetrahydronaphthalenes; D014018:Tissue Distribution; D014105:Tosyl Compounds / Q000737:chemistry
chemical_list: D002700:Chloramines; D007202:Indicators and Reagents; D007457:Iodine Radioisotopes; D010880:Piperidines; D013764:Tetrahydronaphthalenes; D014105:Tosyl Compounds; C016300:chloramine-T; C065043:5-iodobenzovesamicol; D006861:Hydrogen Peroxide; D010463:Peracetic Acid; D010622:Phencyclidine