RT Journal Article
SR Electronic
T1 Delineation of Hypoxia in Canine Myocardium Using PET and Copper(II)-Diacetyl-<em>bis</em>(<em>N</em><sup>4</sup>-Methylthiosemicarbazone)
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1557
OP 1569
VO 43
IS 11
A1 Lewis, Jason S.
A1 Herrero, Pilar
A1 Sharp, Terry L.
A1 Engelbach, John A.
A1 Fujibayashi, Yasuhisa
A1 Laforest, Richard
A1 Kovacs, Attila
A1 Gropler, Robert J.
A1 Welch, Michael J.
YR 2002
UL http://jnm.snmjournals.org/content/43/11/1557.abstract
AB Copper(II)-diacetyl-bis(N4-methylthiosemicarbazone) (copper-ATSM) is a hypoxia-avid tracer for the selective identification of hypoxic tissue. Using canine models of hypoxic myocardium, we report our findings on *Cu-ATSM PET (*Cu is defined as either 60Cu, 61Cu, or 64Cu) for the delineation of ischemic and hypoxic myocardium. Methods: In protocol I, myocardial hypoxia was induced by global hypoxia (n = 3). In protocol II, myocardial ischemia was generated by occlusion of the left anterior descending coronary artery (n = 9). In protocol III, coronary artery stenosis was induced by a stenosis in the left anterior descending coronary artery (n = 4). PET dynamic data were acquired immediately after tracer injection. Tracer retention kinetics were analyzed using either monoexponential analysis (1/kmono) or a simple 2-compartment model (1/k4). Results: In protocol I, tracer retention in hypoxic myocardium was 2-fold greater than in normal myocardium, despite a 7-fold increase in blood flow (normal, 0.70 ± 0.42 mL·min−1·g−1; hypoxic, 4.94 ± 3.00 mL·min−1·g−1 [P &lt; 0.005]). In protocol II, ∼3 h after occlusion, retention of *Cu-ATSM within 20 min was greater in ischemic regions (myocardial blood flow, 0.28 ± 0.26 mL·min−1·g−1) than in normal tissue (myocardial blood flow, 0.52 ± 0.19 mL·min−1·g−1) (1/kmono, 40.72 ± 39.0 min vs. 26.69 ± 22.29 min [P &lt; 0.05]; 1/k4, 6.85 ± 4.90 min vs. 3.51 ± 1.97 min [P &lt; 0.05]). In selected dogs, tracer retention decreased at 24 h, suggesting the development of necrosis with no subsequent retention of *Cu-ATSM. In protocol III, dobutamine infusion after stenosis placement resulted in increased tracer retention consistent with hypoxia in the damaged regions. Conclusion: *Cu-ATSM PET has shown quantitative selective uptake in hypoxic myocardium within 20 min of tracer administration in 3 canine models of hypoxia.