A novel gallium bisaminothiolate complex as a myocardial perfusion imaging agent

Plössl, Karl; Chandra, Rajesh; Qu, Wenchao; Lieberman, Brian P.; Kung, Mei-Ping; Zhou, Rong; Huang, Bin; Kung, Hank F.

doi:10.1016/j.nucmedbio.2007.08.002

« Previous Next »Nuclear Medicine and Biology
Volume 35, Issue 1 , Pages 83-90, January 2008

A novel gallium bisaminothiolate complex as a myocardial perfusion imaging agent

Karl Plössl
- Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA
Rajesh Chandra
- Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA
Wenchao Qu
- Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA
Brian P. Lieberman
- Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA
Mei-Ping Kung
- Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA
Rong Zhou
- Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA
Bin Huang
- Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA
Hank F. Kung
- Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA
- Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA
- Corresponding author. Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA. Tel.: +1 215 662 3096; fax: +1 215 349 5035.

Received 16 June 2007; received in revised form 9 August 2007; accepted 11 August 2007. published online 15 November 2007.

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 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.