Evaluation of gallium-68 tris(2-mercaptobenzyl)amine: A complex with brainand myocardial uptake

Previous research into development of a gallium-radiolabeled agent that cro sses the blood-brain barrier has met with limited success. In this study, w e focused our attention on a Ga(III) complex of a 4-coordinate amine trithi olate tripod ligand, tris(2-mercaptobenzyl) amine (S3N). The Ga(III) S3N co mplex is small, neutral, and lipophilic, meeting the requirements for a pot ential brain imaging agent. The Ga-68 complex was easily formed with a radi ochemical purity of >95%. In vitro stability of the Ga-S3N complex, determi ned in rat serum incubated at 37 degrees C, was greater than 95% intact at 2 h by silica gel and reversed-phase radio-thin layer chromatography, Biodi stribution studies conducted in female Sprague-Dawley rats showed the compl ex cleared rapidly from the blood with initial high liver uptake followed b y rapid washout. Significant uptake was observed in the brain, with brain:b lood ratios increasing from 0.11 at 2 min postinjection to 3.8 at 60 min po stinjection. Uptake was also observed in the heart going from a heart:blood ratio of 2.3 at 2 min postinjection to 11 at 60 min postinjection. Molecul ar mechanics were used to determine the coordination number, and demonstrat ed that the Ga(III) complex prefers to be di-coordinate, Imaging studies wi th Ga-68-S3N in a Nemestrina macaque showed significant brain uptake, simil ar to other lipophilic agents. The extraction of Ga-68-S3N into the brains of both rodents and primates, higher than any Ga-68 agent reported in the l iterature, suggests that this compound may have potential as a brain imagin g agent for positron emission tomography, NUCL MED BIOL 26;3:305-316, 1999. (C) 1999 Elsevier Science Inc. All rights reserved.