Noninvasive detection of hypoxic myocardium using fluorine-18- fluoromisonidazole and positron emission tomography

G. V. Martin, J. H. Caldwell, M. M. Graham, J. R. Grierson, K. Kroll, M. J. Cowan, T. K. Lewellen, J. S. Rasey, J. J. Casciari, K. A. Krohn

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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 noninvasively 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 serial 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 anterior 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 nonischemic regions. Postmortem tissue sampling of Group 1 hearts showed significant FMISO retention in samples 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 blood flow (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.

Original languageEnglish (US)
Pages (from-to)2202-2208
Number of pages7
JournalJournal of Nuclear Medicine
Volume33
Issue number12
StatePublished - Jan 1 1992

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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    Martin, G. V., Caldwell, J. H., Graham, M. M., Grierson, J. R., Kroll, K., Cowan, M. J., Lewellen, T. K., Rasey, J. S., Casciari, J. J., & Krohn, K. A. (1992). Noninvasive detection of hypoxic myocardium using fluorine-18- fluoromisonidazole and positron emission tomography. Journal of Nuclear Medicine, 33(12), 2202-2208.