Myocardial kinetics of fluorine-18 misonidazole: a marker of hypoxic myocardium.
Fluoromisonidazole, a member of a class of compounds referred to as "hypoxic sensitizers," accumulates in hypoxic, viable tumor cells. We hypothesized that it might therefore accumulate also in ischemic, but non-necrotic myocardium potentially salvageable by interventional therapy. To evaluate the myocardial kinetics of [18F]fluoromisonidazole (FM), 20 isolated perfused rabbit hearts were used to characterize the uptake and binding of tracer under control conditions (n = 6), or with ischemia (flow 10% of control, n = 5), hypoxia without low flow (control flow rates with hypoxic medium, n = 5), or with reperfusion (n = 4). Myocardial retention of tracer detected externally with gamma scintillation probes after 20 min of constant [18F]FM infusion followed by 20 min of washout with nonradioactive buffer was 41 +/- 7% and 46 +/- 8% of peak activity in hearts subjected to ischemia or hypoxia, respectively, and significantly higher than in hearts subjected to either control perfusion or to ischemia followed by reperfusion (18 +/- 6 and 16 +/- 5% of peak activity, respectively, p less than 0.01). The biologic half-time of retained tracer was 40 hr in all hearts indicating essentially irreversible binding. Based on these findings, we measured uptake of [18F]FM using positron emission tomography in five dogs subjected to acute coronary occlusion. Five to thirteen millicuries of tracer were injected within 3 hr of occlusion. Within 30 min after administration of tracer, 18F accumulation in ischemic myocardium was greater than that observed in normal myocardium. The results indicate that [18F]FM accumulates in ischemic myocardium in relation to diminished tissue oxygen content and not simply because of diminished flow. Thus, this class of compounds may be potentially useful to help identify hypoxic myocardium.
Shelton
M E
ME
Department of Internal Medicine Washington University School of Medicine, St. Louis, Missouri 63110.
Dence
C S
CS
Hwang
D R
DR
Welch
M J
MJ
Bergmann
S R
SR
D000818:Animals; D003327:Coronary Disease / Q000000981:diagnostic imaging / Q000378:metabolism*; D004285:Dogs; D005462:Fluorine Radioisotopes; D000860:Hypoxia / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D008920:Misonidazole / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D009206:Myocardium / Q000378:metabolism*; D011817:Rabbits; D011877:Radionuclide Imaging
D005462:Fluorine Radioisotopes; D008920:Misonidazole