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There is a great interest in obtaining a compound labeled with technetium which would distribute in the brain as a function of blood flow and have a retention which is sufficient to allow for good imaging. It has been shown that WmTc(V)-oxo complexes of aminederivatized diamine-dithiol (DADT) ligands cross the blood-brain barrier and are retained in the brain (1). The retention of these compounds in the brain is not sufficient to allow for routine use in imaging regional cerebral blood flow (rCBF). In addition, the aminederivatized DADT complexes show selective hippocampal localization at 30 min. post injection (2).In our quest for a 99mTc agent for imaging rCBF, we considered several potential mechanisms which would provide adequate retention for imaging without perturbing the distribution as a function of flow. A clean, well-characterized in vivo chemical transformation of a lipophilic complex into a species which would be trapped in the brain would provide these characteristics. Esterases are known to exist in the brain, so the hydrolysis of an ester into a carboxylic acid was one targeted approach. DADT ligands were synthesized which incorporated esters on the ligand backbone (Figure 1, 1). The corresponding 99mTc(V)-oxo complexes were prepared by ligand exchange with WmTcglucoheptonate and evaluated in rats and primates as potential brain perfusion 1 2 Figure 1 imaging agents. One of these complexes, the 9gmTc complex of N, N'-l,2-ethylenediylbis-L-cysteine diethyl ester (99mTc-L,L-ECD, 2), showed excellent uptake and retention characteristics in primate imaging studies. The retention mechanism appears to be stereospecific with respect to the ligand ( Table 1). The L,L-ECD complex is retained effectively, while the D,D form has a much faster

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