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

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 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.

• Authors: 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
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 33 Issue 12 Pg. 2202-8 (Dec 1992) ISSN: 0161-5505 [Print] United States
• PMID: 1460516 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Fluorine Radioisotopes
• fluoromisonidazole
• Misonidazole

Topics

• Animals
• Dogs
• Fluorine Radioisotopes
• Misonidazole (analogs & derivatives)
• Myocardial Ischemia (diagnostic imaging)
• Myocardium (metabolism)
• Tomography, Emission-Computed