New ^99mTc Radiotracers for Myocardial Perfusion Imaging by SPECT

Myocardial Perfusion Imaging (MPI) with radiotracers is an integral component in evaluation of the patients with known or suspected coronary artery diseases (CAD). 99mTc-Sestamibi and 99mTc-Tetrofosmin are commercial radiopharmaceuticals for MPI by single photon-emission computed tomography (SPECT). Despite their widespread clinical applications, they do not meet the requirements of an ideal perfusion imaging agent due to their inability to linearly track the regional myocardial blood flow rate at >2.5 mL/min/g. With tremendous development of CZT-based SPECT cameras over the past several years, the nuclear cardiology community has been calling for better perfusion radiotracers with improved extraction and biodistribution properties.

This review will summarize recent research efforts on new cationic and neutral 99mTc radiotracers for SPECT MPI. The goal of these efforts is to develop a 99mTc radiotracer that can be used to detect perfusion defects at rest or under stress, determine the regional myocardial blood flow, and measure the perfusion and left ventricular function.

The advantage of cationic radiotracers (e.g. 99mTc-Sestamibi) is their long myocardial retention because of the positive molecular charge and fast liver clearance kinetics. 99mTc-Teboroxime derivatives have a high initial heart uptake (high first-pass extraction fraction) due to their neutrality. 99mTc- 3SPboroxime is the most promising radiotracer for future clinical translation considering its initial heart uptake, myocardial retention time, liver clearance kinetics, heart/liver ratios and SPECT image quality.

99mTc-3SPboroximine is an excellent example of perfusion radiotracers, the heart uptake of which is largely relies on the regional blood flow. It is possible to use 99mTc-3SPboroximine for detection of perfusion defect(s), accurate quantification and determination of regional blood flow rate. Development of such a 99mTc radiotracer is of great clinical benefit for accurate diagnosis of CAD and assessing the risk of future hard events (e.g. heart attack and sudden death) in cardiac patients.