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Noninvasive Detection of Hypoxic Myocardium Using Fluorine-18-Fluoromisonidazole and Positron Emission Tomography

Division of Cardiology, Seattle VA Medical Center, and the Departments of Radiology, Bioengineering, Physiological Nursing and Radiation Oncology, University of Washington, Seattle, Washington

Correspondence: For reprints contact: Gary V. Martin, MD, Department of Cardiology (111c), Veterans Administration Medical Center, 1660 South Columbian Way, Seattle, WA 98108.

ABSTRACT

Fluoromisonidazole (FMISO) is metabolically trapped in viable cells as a function of reduced cellular pO₂. Therefore [¹⁸F]-FMISO is potentially useful for evaluating patients with hypoxic but viable myocardium. The goal of this study was to investigate [¹⁸F]FMISO uptake in ischemic myocardium non-invasively using positron emission tomography (PET). Studies were performed in 10 open-chest dogs subjected to either complete (Group 1, n = 5) or partial (Group 2, n = 5) occlusion of the left anterior descending coronary artery. The tracer was administered by intravenous bolus following the onset of ischemia and senal PET images were acquired for the next 4 hr. In Group 1, viability was assessed using histochemical staining (nitroblue tetrazolium, NBT) and ^99mTc-pyrophosphate (Tc-PYP). In Group 2, viability was assessed using measurements of regional wall motion, histochemical staining and histology (two animals). In each study, PET images obtained at times between 2 and 4 hr postinjection showed specific enhancement of tracer activity in the distal interior wall and apex of the left ventricle. At 4 hr, the tissue-to-blood pool count ratio was significantly higher in ischemic regions; 1.8 ± 0.4 for Group 1 and 1.6 ± 0.2 for Group 2 versus 1.0 ± 0.1 in non ischemic regions. Postmortem tissue sampling of Group 1 hearts showed significant FMISO retention in sampIes without evidence for infarction, either by NBT or Tc-PYP deposition, as well as in more severely ischemic regions. In Group 2 animals, FMISO was retained in myocardial regions with reduced bloodflow (microspheres), which exhibited improved contraction following reperfusion. We conclude that PET imaging of [¹⁸F]FMISO is a promising technique for the noninvasive identification of viable hypoxic myocardium.

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