A novel gallium bisaminothiolate complex as a myocardial perfusion imaging agent

The development of new myocardial perfusion imaging agents for positron emission tomography (PET) may improve the resolution and quantitation of changes in regional myocardial perfusion measurement. It is known that a 68Ge/68Ga generator can provide a convenient source of PET tracers because of the long physical half-life of 68Ge (271 days). A new ligand, 7,8-dithia-16,24-diaza-trispiro[5.2.5.2.5.3]pentacosa-15,24-diene, which consists of a N2S2-chelating core incorporated into three cyclohexyl rings, was prepared. To test feasibility and potential utility, the N2S2 ligand was successfully labeled and tested with 67Ga (half-life=3.26 day; γ=93.3, 184.6 and 300.2 keV), which showed >92% radiochemical purity. The corresponding “cold” Ga complex was synthesized, and its structure containing a pyramidal N2S2 chloride core was elucidated with X-ray crystallography. In vivo biodistribution of this novel 67Ga complex, evaluated in normal rats, exhibited excellent heart uptake and retention, with 2.1% and 0.9% initial dose/organ at 2 and 60 min, respectively, after an intravenous injection. Autoradiography was performed in normal rats and in rats that had the left anterior descending coronary artery permanently ligated surgically. Autoradiography showed an even uptake of activity in the normal heart, and there was a distinctively lower uptake in the damaged side of the surgically modified heart. In conclusion, the new N2S2 ligand was readily prepared and labeled with radioactive 67Ga. Biodistribution in rats revealed high initial heart uptake and relatively high retention reflecting regional myocardial perfusion.