Hosokawa R, Nohara R, Fujibayashi Y, Okuda K, Ogino M, Hata T, Fujita M, Tamaki N, Konishi J, Sasayama S
Department of Internal Medicine, Kyoto University Hospital, and Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
J Nucl Med. 1997 Dec;38(12):1857-63.
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.
为评估123I-（ρ-碘苯基）-3-R，S-甲基十五烷酸（123I-BMIPP）对缺血性心脏病的临床应用价值，我们在轻度和重度缺血犬模型中研究了123I-BMIPP的代谢转归，并评估了该示踪剂的临床应用价值。
在麻醉下使用开胸犬，我们组装了一个系统，必要时可使大冠状静脉中的所有血液流出且不再循环。向左前降支冠状动脉注射BMIPP后，在缺血10分钟（轻度缺血，5只犬）、缺血30分钟（重度缺血，6只犬）、再灌注后以及正常对照组（6只犬）期间，从冠状静脉和腹主动脉采集血液样本。使用高效液相色谱法评估BMIPP的分解代谢产物，包括未代谢BMIPP的反向扩散。
尽管三组中BMIPP从血浆快速摄取到心肌并随后潴留的情况未变，但重度缺血时放射性的早期洗脱（8分钟时）显著增加（从50%±13%增至61%±8%；p<0.05）。心肌中的代谢产物包括未代谢BMIPP的反向扩散以及α-氧化、中间氧化和完全氧化代谢产物。对于轻度缺血，尽管代谢产物的各自比例有一些变化，但这些值与正常对照组相比无显著改变。轻度缺血再灌注后的乳酸生成（表明缺血的严重程度）与BMIPP的反向扩散水平（r=-0.92）和完全氧化代谢产物（r=0.78）密切相关。另一方面，对于重度缺血，未代谢BMIPP 的反向扩散水平增加（从25.1%±8.0%增至34.7%±8.7%；p<0.05），而完全氧化代谢产物减少（从21.4%±10.9%降至14.8%±7.3%）。
BMIPP的代谢与心肌缺血的严重程度密切相关。因此，123I-BMIPP可能是一种用于评估缺血性心脏病的有前景且敏感的放射性药物。
