Minimizing liver uptake of cationic 99mTc radiotracers with ether and crown ether functional groups

Abstract

Ischemia-related diseases, particularly coronary artery disease (CAD), account for the majority of deaths worldwide. Myocardial ischemia is a serious condition and the delay in reperfusion of ischemic tissues can be life-threatening. This is particular true in the aged population. Rapid and accurate early detection of myocardial ischemia is highly desirable so that various therapeutic regiments can be given before irreversible myocardial damage occurs. Myocardial perfusion imaging with radiotracers is an integral component in evaluations of patients with known or suspected CAD. (99m)Tc-Sestamibi and (99m)Tc-Tetrofosmin are commercial radiopharmaceuticals currently available for myocardial perfusion imaging. Despite their widespread clinical applications, both (99m)Tc-Sestamibi and (99m)Tc-Tetrofosmin do not meet the requirements of an ideal perfusion imaging agent, largely due to their high liver uptake. The intense liver uptake makes it difficult to interpret the heart activity in the inferior and left ventricular wall. Photon scattering from the high liver radioactivity accumulation remains a significant challenge for diagnosis of heart diseases. This review will summarize the most recent research efforts to minimize the liver uptake of cationic (99m)Tc radiotracers by using ether and crown ether-containing chelators. Fast liver clearance will shorten the duration of imaging protocols (< 30 min post-injection), and allow for early acquisition of heart images with high quality. Improvement of heart/liver ratio may permit better detection of the presence and extent of coronary artery disease. Identification of such a new radiotracer that allows for the improved noninvasive assessment of myocardial perfusion would be of considerable benefit in treatment of patients with suspected CAD.