Myocardial kinetics of iodine-123-BMIPP in canine myocardium after regional ischemia and reperfusion: implications for clinical SPECT.

To evaluate the clinical utility of 123I-(rho-iodophenyl)-3-R,S-methylpentadecanoic acid (123I-BMIPP) for ischemic heart disease, we investigated the metabolic fate of 123I-BMIPP in canine models with mild and severe ischemia and evaluated the clinical utility of this tracer. Using open-chest dogs under anesthesia, we assembled a system that would release all the blood from the great cardiac vein without recirculation, if necessary. After injection of BMIPP into the left anterior descending coronary artery, blood samplings from cardiac vein and abdominal aorta were performed for 10-min ischemia (mild ischemia, five dogs) and 30-min ischemia (severe ischemia, six dogs), after reperfusion and for normal controls (six dogs). The catabolites of BMIPP, including backdiffusion of nonmetabolized BMIPP, were evaluated using high-performance liquid chromatography. Although the rapid extraction of BMIPP from the plasma into the myocardium and the subsequent retention were unchanged among three groups, the early washout (at 8 min) of radioactivity significantly increased (from 50% +/- 13% to 61% +/- 8%; p < 0.05) in severe ischemia. The metabolites from the myocardium consisted of backdiffusion of nonmetabolized BMIPP and alpha-oxidation, intermediate-oxidation and full-oxidation metabolites. For mild ischemia, these values were not significantly changed from the normal control, although the respective proportions of metabolites showed some variation. Lactate production after reperfusion on mild ischemia, which indicates the severity of ischemia, was closely correlated with the level of backdiffusion of BMIPP (r = -0.92) and the full-oxidation metabolite (r = 0.78). On the other hand, for severe ischemia, the level of backdiffusion of nonmetabolized BMIPP increased (from 25.1% +/- 8.0% to 34.7% +/- 8.7%; p < 0.05), and the full-oxidation metabolites decreased (from 21.4% +/- 10.9% to 14.8% +/- 7.3%). The metabolism of BMIPP was closely associated with the severity of myocardial ischemia. Thus, 123I-BMIPP might be a promising and sensitive radiopharmaceutical for the evaluation of ischemic heart disease.