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99mTc-HL91: "hot spot" detection of ischemic myocardium in vivo by gamma camera imaging
R D Okada1, G Johnson, K N Nguyen
1William K. Warren Medical Research Institute of the University of Oklahoma Health Sciences Center, Tulsa 74136, USA.
Insights
This study shows that 99mTc-HL91 can detect regional myocardial ischemia in vivo using gamma camera imaging. This new hypoxia imaging agent identifies ischemic tissue within 15 minutes.
Area of Science:
- Nuclear Medicine
- Cardiovascular Imaging
- Radiopharmaceutical Development
Background:
- 99mTc-HL91 is a novel hypoxia imaging agent.
- It shows increased uptake and retention in hypoxic myocardium in vitro.
- Its ability to detect regional ischemia in vivo requires investigation.
Purpose of the Study:
- To determine if 99mTc-HL91 can detect regional myocardial ischemia in vivo.
- To evaluate its efficacy using gamma camera imaging.
Main Methods:
- Eight dogs underwent induced left circumflex (LCx) stenoses.
- 99mTc-HL91 and microspheres were injected, followed by 4-hour gamma camera imaging.
- Heart slices were analyzed, stained with TTC, and tissues were counted.
Main Results:
- "Hot spots" indicating ischemia were detected in all 8 dogs within 60 minutes.
- LCx/LAD activity ratios increased significantly within 30 minutes (final ratio, 3.0; P<0.05).
- Significant differences in washout curves were observed within 15 minutes, with higher retention in ischemic regions (LCx vs. LAD, P<0.01).
Conclusions:
- 99mTc-HL91 successfully identifies regional myocardial ischemia in a canine model.
- Quantitative imaging techniques enable detection of ischemic myocardium within 15 minutes of tracer administration.
Background:
99mTc-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 99mTc-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 99mTc-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 x min(-1) x g(-1), and mean left anterior descending coronary artery (LAD) flow was 0.96+/-0.02 mL x min(-1) x 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 x min(-1) x g(-1)) had an inverse linear correlation (r= -0.80); phase 2, (flow, >0.7 mL x min(-1) x g(-1)) had no correlation. Ischemic heart/liver ratios remained near 1.0 for 4 hours.
Conclusions:
99mTc-HL91 positively identifies regional myocardial ischemia in a canine model using 99mTc imaging. Quantitative techniques allowed identification of ischemic myocardium within 15 minutes of tracer administration.