Monocationic radiotracer kinetics and myocardial infarct size: A perfused rat heart study

Objective: To compare the myocardial kinetics of three ^99mtechnetium-labeled monocationic tracers [methoxy- isobutylisonitrile (MIBI), tetrofosmin, and Q12] in a model of ischemia-reperfusion (IR) to determine their abilities to assess myocardial viability. Methods: Isolated perfused rat hearts (n = 30) were studied in control and IR groups for each tracer. IR hearts were treated with 120 min global no-flow followed by 5 min reflow, then 60 min tracer uptake/clearance. Tracer kinetics were monitored using a scintillation detector. Results: This model produced significant myocardial injury, without significant differences in the percentage of injured myocardium by triphenyltetrazolium chloride (TTC) staining and creatine kinase (CK) assay. Transmission electron microscopy analysis also confirmed necrosis with abundant mitochondrial damage in the IR hearts. All three IR groups exhibited significantly less mean (±standard error of the mean) tracer retention than matched controls (MIBI 73.4 ± 4.9% vs. 96.9 ± 1.76%, tetrofosmin 38.7 ± 4.6% vs. 82.2 ± 3.5%, and Q12 23.0 ± 2.5% vs. 43.8 ± 1.8%, respectively; P < 0.05). Tetrofosmin IR hearts exhibited 54 ± 9% of control myocardial retention, which was significantly less than either MIBI (86 ± 5%, P < 0.05) or Q12 (63 ± 6%, P < 0.05); thus, tetrofosmin provided the best differentiation between nonviable and normal myocardium. Furthermore, tetrofosmin end activity (%id/g) in controls was significantly higher than Q12 (4.09 ± 0.04 vs. 1.71 ± 0.06, respectively, P < 0.05), and tetrofosmin end activity (%id/g) in IR hearts was significantly higher than Q12 (2.19 ± 0.37 vs. 1.06 ± 0.12, respectively, P < 0.05). The correlation between end activity and viable myocardium determined by TTC staining was r = 0.66 (P < 0.05) for MIBI, r = 0.94 (P < 0.05) for tetrofosmin, and r = 0.91 (P < 0.05) for Q12. The correlation between myocardial end activity and myocardial CK leak was r = -0.62 (P < 0.05) for MIBI, r = -0.87 (P < 0.05) for tetrofosmin, and r = -0.89 (P < 0.05) for Q12. Conclusions: Nonviable myocardium can be distinguished from normal myocardium by the retention kinetics of all three monocationic tracers studied. Tetrofosmin and Q12 end activities demonstrate the best correlation with infarct size. However, tetrofosmin kinetics may combine the greatest differentiation between nonviable and normal myocardium, while still retaining adequate activity for imaging.