99mTc-3SPboroxime: A neutral 99mTc(III) radiotracer with high heart uptake and long myocardial retention

Abstract

Background99mTc-3SPboroxime is a 99mTc(III) complex with high initial heart uptake comparable to that of 99mTc-Teboroxime, but with significantly longer myocardial retention in Sprague–Dawley rats. This study was performed to demonstrate its feasibility on myocardial perfusion imaging and myocardial blood flow quantification in swine models. MethodsDynamic single-photon emission computed tomography (SPECT) studies with 99mTc-3SPboroxime were performed in normal (with/without dipyridamole, n = 9) and acute myocardial infarction (AMI) swine (n = 3) in comparison with 99mTc-Teboroxime and 99mTc-Sestamibi. List-mode acquisitions were immediately started after injection and continued for 15 minutes. Regions of interest were drawn on heart (infarct and remote areas of AMI swine) and liver to generate time activity curves. Heart/liver and infarct/remote radioactivity ratios were calculated. One-tissue compartment model was implemented to obtain K1 and K2 values. ResultsThe initial heart uptake of 99mTc-3SPboroxime was close to that of 99mTc-Teboroxime, but higher than that of 99mTc-Sestamibi. 99mTc-3SPboroxime had a myocardial retention longer than that of 99mTc-Teboroxime. The heart/liver ratio of 99mTc-3SPboroxime was higher than that of 99mTc-Teboroxime at later stage (13-15 minutes post-injection). The K1 value of 99mTc-3SPboroxime was much higher than that of 99mTc-Sestamibi, and the K2 value was significantly lower than that of 99mTc-Teboroxime both at rest and dipyridamole stress (rest K1: 0.63 ± 0.11 vs 0.40 ± 0.04 mL·min−1·g−1, P = 0.027; stress K1: 0.89 ± 0.05 vs 0.54 ± 0.08 mL·min−1·g−1, P = 0.031; rest K2: 0.22 ± 0.04 vs 0.33 ± 0.11 mL·min−1·g−1, P = 0.003; stress K2: 0.31 ± 0.03 vs 0.60 ± 0.30 mL·min−1·g−1, P = 0.047). High quality SPECT images could be obtained in any of the 5 minutes windows over the first 15 minutes after injection of 99mTc-3SPboroxime in normal and AMI swine models. Apical and anterior perfusion defects were clearly visualized in AMI swine. Conclusion99mTc-3SPboroxime is a promising radiotracer for future clinical translation considering its heart uptake, heart/liver ratio and SPECT image quality, as well as the advantage over 99mTc-Sestamibi in the definition of stress flow.