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 neuromuscu lar 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]glucohepto nate gave a 4.7:1 mixture of two Tc-99m complexes as determined by HPL C. 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 th e highest uptake. For whole brain, the % injected dose values were 0.2 7, 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-aminoben zovesamicol. The low brain uptake of [Tc-99m]-1 vs 5-iodobenzovesamico l is attributed to its higher molecular weight (752) and lower binding affinity.