Background-Tc-99m-HL91 is a new hypoxia imaging agent that demonstrate
s increased uptake and retention in globally hypoxic myocardium in vit
ro. The purpose of this study was to determine whether Tc-99m-HL91 cou
ld detect regional ischemia in vivo by gamma camera imaging. Methods a
nd Results-Eight open-chest dogs with left circumflex (LCx) stenoses w
ere studied. Injection of 5 mCi of Tc-99m-HL91 and microspheres was fo
llowed by imaging over 4 hours. Heart slices were imaged, then stained
with triphenyltetrazolium chloride (TTC), and tissues were well-count
ed. TTC staining demonstrated no injury. Mean LCx blood flow was 0.32
+/- 0.04 mL . min(-1) . g(-1), and mean left anterior descending coron
ary 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 m
inutes (final ratio, 3.0; P<0.05). LCx and LAD washout curves demonstr
ated significant differences within 15 minutes. Washout curves were bi
exponential over 1 hour, followed by linear retention from 1 to 4 hour
s, 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: ph
ase 1 (flow, 0.05 to 0.7 mL . min(-1) . g(-1)) had an inverse linear c
orrelation (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 ho
urs. Conclusions-Tc-99m-HL91 positively identifies regional myocardial
ischemia in a canine model using Tc-99m imaging. Quantitative techniq
ues allowed identification of ischemic myocardium within 15 minutes of
tracer administration.