title: 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.affiliation: Division of Cardiology, Seattle VA Medical Center, WA 98108.
authors.forename: G V
authors.initials: GV
authors.lastname: Martin
authors.forename: J H
authors.initials: JH
authors.lastname: Caldwell
authors.forename: M M
authors.initials: MM
authors.lastname: Graham
authors.forename: J R
authors.initials: JR
authors.lastname: Grierson
authors.forename: K
authors.initials: K
authors.lastname: Kroll
authors.forename: M J
authors.initials: MJ
authors.lastname: Cowan
authors.forename: T K
authors.initials: TK
authors.lastname: Lewellen
authors.forename: J S
authors.initials: JS
authors.lastname: Rasey
authors.forename: J J
authors.initials: JJ
authors.lastname: Casciari
authors.forename: K A
authors.initials: KA
authors.lastname: Krohn
mesh_terms: D000818:Animals; D004285:Dogs; D005462:Fluorine Radioisotopes; D008920:Misonidazole / Q000031:analogs & derivatives*; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging*; D009206:Myocardium / Q000378:metabolism*; D014055:Tomography, Emission-Computed
chemical_list: D005462:Fluorine Radioisotopes; C031843:fluoromisonidazole; D008920:Misonidazole