title: Synthesis and in vivo evaluation of a 99m/99Tc-DADT-benzovesamicol: a potential marker for cholinergic neurons.
abstract: The diaminodithiol (DADT) ligand has been conjugated to the neuromuscular blocking agent benzovesamicol (BVM) in the 5-position. DADT-BVM 1 was synthesized by coupling of 5-aminomethylbenzovesamicol with a BCA thiolactone reagent. 99mTc radiolabeling of 1 with [99mTc]glucoheptonate gave a 4.7:1 mixture of two 99mTc complexes as determined by HPLC. Biodistribution data of the major [99mTc]-1 complex in CD-1 mice (n = 4-5) showed very little uptake and no regional selectivity in the mouse brain. At all time points examined, the lung and liver showed the highest uptake. For whole brain, the % injected dose values were 0.27, 0.12, 0.04 and 0.01% at t = 1, 5, 30 and 240 min. The major [99mTc]-1 product exhibited a log P = 3.13 +/- 0.06 (SD) with an IC50 = 140-280 nM for the corresponding [99Tc]-1 vs (-)-N-[3H]methyl-5-aminobenzovesamicol. The low brain uptake of [99mTc]-1 vs 5-iodobenzovesamicol is attributed to its higher molecular weight (752) and lower binding affinity.
authors.affiliation: Division of Nuclear Medicine, University of Michigan Medical Center, Ann Arbor 48109-0552, USA.
authors.forename: R B
authors.initials: RB
authors.lastname: del Rosario
authors.forename: Y W
authors.initials: YW
authors.lastname: Jung
authors.forename: K E
authors.initials: KE
authors.lastname: Baidoo
authors.forename: S Z
authors.initials: SZ
authors.lastname: Lever
authors.forename: D M
authors.initials: DM
authors.lastname: Wieland
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D005069:Evaluation Studies as Topic; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000378:metabolism; D014781:Viscera / Q000378:metabolism
chemical_list: D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C107949:technetium Tc 99m diaminodithiol-benzovesamicol