Evaluation of gallium-68 tris(2-mercaptobenzyl)amine: a complex with brain and myocardial uptake

• Published in: Nuclear medicine and biology Vol. 26; no. 3; pp. 305 - 316
• Main Authors: Cutler, Cathy S, Giron, M.Cecilia, Reichert, David E, Snyder, Abraham Z, Herrero, Pilar, Anderson, Carolyn J, Quarless, Duncan A, Koch, Stephen A, Welch, Michael J
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.04.1999; Elsevier
• Subjects: 68Ga-S 3N; Animals; Autoradiography; Biological and medical sciences; Blood-Brain Barrier - physiology; Brain - diagnostic imaging; Brain - metabolism; Brain imaging agent; Carbon Radioisotopes; Contrast media. Radiopharmaceuticals; Cricetinae; Dogs; Drug Stability; Ethanol - pharmacokinetics; Female; Ga(III); Gallium Radioisotopes - chemistry; Heart - diagnostic imaging; Heart imaging agent; Imaging; Lung - diagnostic imaging; Lung - metabolism; Macaca nemestrina; Male; Medical sciences; Mesocricetus; Myocardium - metabolism; Organometallic Compounds - blood; Organometallic Compounds - chemical synthesis; Organometallic Compounds - pharmacokinetics; Pharmacology. Drug treatments; Radiopharmaceuticals - blood; Radiopharmaceuticals - chemical synthesis; Radiopharmaceuticals - pharmacokinetics; Rats; Rats, Sprague-Dawley; Thiosemicarbazones - pharmacokinetics; Tissue Distribution; Tomography, Emission-Computed; Ga(III); Brain imaging agent; 68Ga-S 3N; Imaging; Heart imaging agent; Macaca nemestrina; Stability; Rat; Rodentia; Central nervous system; Vertebrata; Mammalia; Gallium III; Animal; Distribution; Primates; Simioidea; Myocardium; Medical imagery; Circulatory system; Radiopharmaceuticals; Brain (vertebrata)
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/S0969-8051(98)00108-5

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 (S 3N). The Ga(III) S 3N 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-S 3N complex, determined in rat serum incubated at 37°C, was greater than 95% intact at 2 h by silica 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 68Ga-S 3N in a Nemestrina macaque showed significant brain uptake, similar to other lipophilic agents. The extraction of 68Ga-S 3N into the brains of both rodents and primates, higher than any 68Ga agent reported in the literature, suggests that this compound may have potential as a brain imaging agent for positron emission tomography.