Technetium-99m dithiocarbamates as potential agents for brain imaging

Thallium-201 diethyldithiocarbamate (DDC) behaves like a chemical microsphere and is trapped by spontaneous decomposition in the brain in proportion to regional perfusion. They have shown that the technetium-99m analog, Tc-99m DDC (1), is unsuitable for cerebral perfusion imaging because it does not decompose rapidly enough to be trapped in the brain. With the goal of turning this greater stability of 1 into an advantage, a series of dithiocarbamates with lipophilic or amine groups designed to enhance cerebral uptake and retention was prepared from the following amines by reaction with carbon disulfide and sodium hydroxide: pyrrolidine (2), piperazine (3), 4-benzylpiperazine (4), and 4-(1-piperidino)piperidine (5). These ligands (5 mg) were labelled with Tc-99m in > 95% efficiency (ITLC-SG, saline) by reduction of pertechnetate at room temperature with formamidine sulfinic acid at alkaline pH. In preliminary studies, 4 and 5 show a trend of increasing oil/buffer partition coefficient with increasing pH as do other brain imaging agents