Evaluation of Gallium-68 Tris(2-Mercaptobenzyl)Amine: A Complex with Brain and Myocardial Uptake

Previous research into development of a gallium-radiolabeled agent that crosses the blood- brain barrier has met with limited success. In this study, we focused our attention on a Ga(III) complex of a 4-coordinate amine trithiolate tripod ligand, tris(2-mercaptobenzyl) amine (S3N). The Ga(III) S3N complex is small, neutral, and lipophilic, meeting the requirements for a potential brain imaging agent. The Ga-68 complex was easily formed with a radiochemical purity of >95%. In vitro stability of the Ga-S3N complex, determined in rat serum incubated at 37°C, was greater than 95% intact a t2hb ysilica gel and reversed-phase radio-thin layer chromatography. Biodistribution studies conducted in female Sprague- Dawley rats showed the complex cleared rapidly from the blood with initial high liver uptake followed by rapid washout. Significant uptake was observed in the brain, with brain:blood ratios increasing from 0.11 at 2 min postinjection to 3.8 at 60 min postinjection. 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. Molecular mechanics were used to determine the coordination number, and demonstrated that the Ga(III) complex prefers to be 4-coordinate. Imaging studies with 68 Ga-S3N in a Nemestrina macaque showed significant brain uptake, similar to other lipophilic agents. The extraction of 68 Ga-S3N into the brains of both rodents and primates, higher than any 68 Ga agent reported in the literature, suggests that this compound may have potential as a brain imaging agent for positron emission tomography. NUCL MED BIOL 26;3:305-316, 1999. © 1999 Elsevier Science Inc. All rights reserved.