A novel gallium bisaminothiolate complex as a myocardial perfusion imaging agent

• Published in: Nuclear medicine and biology 2008-01, Vol.35 (1), p.83-90
• Main Authors: Plössl, Karl, Chandra, Rajesh, Qu, Wenchao, Lieberman, Brian P, Kung, Mei-Ping, Zhou, Rong, Huang, Bin, Kung, Hank F
• Format: Article
• Language: English
• Subjects: 67/68Ga labeling; Animals; Autoradiography; Coronary Circulation; Gallium Radioisotopes; Heart - diagnostic imaging; In vivo biodistribution; Isotope Labeling; Male; Myocardial Infarction - diagnostic imaging; Myocardial perfusion; PET imaging; Positron-Emission Tomography; Radiology; Radiopharmaceuticals; Rats; Rats, Sprague-Dawley; Tomography, Emission-Computed, Single-Photon
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/j.nucmedbio.2007.08.002

Abstract 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 a68 Ge/68 Ga generator can provide a convenient source of PET tracers because of the long physical half-life of68 Ge (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 N2 S2 -chelating core incorporated into three cyclohexyl rings, was prepared. To test feasibility and potential utility, the N2 S2 ligand was successfully labeled and tested with67 Ga (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 N2 S2 chloride core was elucidated with X-ray crystallography. In vivo biodistribution of this novel67 Ga 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 N2 S2 ligand was readily prepared and labeled with radioactive67 Ga. Biodistribution in rats revealed high initial heart uptake and relatively high retention reflecting regional myocardial perfusion.