Synthesis of new bis(aminoethanethiol) (BAT) derivatives: possible ligands for 99mTc brain imaging agents.

In developing new brain perfusion imaging agents for single photon emission computed tomography (SPECT), five 99mTc-labeled neutral bis(aminoethanethiol) (BAT) derivatives capable of crossing the blood-brain barrier are reported. The five ligands are prepared by two versatile synthetic methods that can specifically introduce substituents on one of the carbons between two nitrogens. These ligands formed stable and neutral complexes with the reduced 99mTc, using either Sn(II) or sodium borohydride to reduce sodium [99mTc]pertechnetate. The biodistribution in rats was evaluated with [125I]iodoantipyrine, a freely diffusible tracer, as the internal reference. Compounds with a free hydroxyl group, 6 and 15, showed lower brain uptake. High initial brain uptake was observed for compounds 10 and 14, 1.28 and 2.30% dose/organ, respectively. Compounds of this type may be used as a basis for future structural modification to improve brain uptake and retention.