SYNTHESIS AND IN-VIVO EVALUATION OF A TC-99M/99-DADT-BENZOVESAMICOL - A POTENTIAL MARKER FOR CHOLINERGIC NEURONS

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. Tc-99m radiolabeling of 1 with [Tc-99m]glucoheptonate gave a 4.7:1 mixture of two Tc-99m complexes as determined by HPLC. Biodistribution data of the major [Tc-99m]-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 [Tc-99m]-1 product exhibited a log P = 3.13 +/- 0.06 (SD) with an IC50 = 140-280 nM for the corresponding [Tc-99]-1 vs (-)-N-[H-3]methyl-5-aminobenzovesamicol. The low brain uptake of [Tc-99m]-1 vs 5-iodobenzovesamicol is attributed to its higher molecular weight (752) and lower binding affinity.