99m Tc-HL91

Abstract

Background — 99m Tc-HL91 is a new hypoxia imaging agent that demonstrates increased uptake and retention in globally hypoxic myocardium in vitro. The purpose of this study was to determine whether 99m Tc-HL91 could detect regional ischemia in vivo by gamma camera imaging. Methods and Results —Eight open-chest dogs with left circumflex (LCx) stenoses were studied. Injection of 5 mCi of 99m Tc-HL91 and microspheres was followed by imaging over 4 hours. Heart slices were imaged, then stained with triphenyltetrazolium chloride (TTC), and tissues were well-counted. TTC staining demonstrated no injury. Mean LCx blood flow was 0.32±0.04 mL · min −1 · g −1 , and mean left anterior descending coronary artery (LAD) flow was 0.96±0.02 mL · min −1 · g −1 (ratio, 0.33). “Hot spots” were detected in 8 of 8 experiments in vivo within 60 minutes and improved over 4 hours. Region of interest analysis of LCx/LAD activity ratios demonstrated significant increases within 30 minutes (final ratio, 3.0; P <0.05). LCx and LAD washout curves demonstrated significant differences within 15 minutes. Washout curves were biexponential over 1 hour, followed by linear retention from 1 to 4 hours. Four-hour fractional retention was 0.12 for LAD and 0.44 for LCx ( P <0.01). Myocardial flow versus tracer uptake demonstrated 2 phases: phase 1 (flow, 0.05 to 0.7 mL · min −1 · g −1 ) had an inverse linear correlation ( r =−0.80); phase 2, (flow, >0.7 mL · min −1 · g −1 ) had no correlation. Ischemic heart/liver ratios remained near 1.0 for 4 hours. Conclusions — 99m Tc-HL91 positively identifies regional myocardial ischemia in a canine model using 99m Tc imaging. Quantitative techniques allowed identification of ischemic myocardium within 15 minutes of tracer administration.