Hosokawa R, Nohara R, Fujibayashi Y, Okuda K, Ogino M, Hirai T, Fujita M, Tamaki N, Konishi J, Sasayama S
Department of Cardiovascular Medicine and Nuclear Medicine, Graduate School of Medicine, and Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
J Nucl Med. 1999 Mar;40(3):471-8.
123I-(rho-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) is a fatty acid analog for SPECT imaging. This radiopharmaceutical possesses the unique property, that is, perfusion-metabolism mismatch on SPECT images in patients with ischemic heart disease. However, the reason of this mechanism remains unclear.
Using open-chest dogs under anesthesia, we made a system to release all the blood of the great cardiac vein outside without recirculation, if necessary. Left anterior descending artery (LAD) was occluded for 30 min after reperfusion. After the injection of BMIPP into LAD, blood samplings from the cardiac vein and abdominal aorta (6 dogs) or serial biopsy specimens from the LAD region (5 dogs) were performed, and then compared with the normal control. The catabolites of BMIPP, including backdiffusion of nonmetabolized BMIPP, were evaluated with high-performance liquid chromatography (HPLC) in the efflux study. Thin-layer chromatography (TLC) technique was introduced in the tissue analytical study.
Although the rapid extraction of BMIPP from the plasma into the myocardium and the subsequent retention were unchanged, the early washout (8 min) of radioactivity significantly increased (51% +/- 12% to 65% +/- 7%; P < 0.05) with ischemia. The metabolites from the myocardium consisted of backdiffusion of nonmetabolized BMIPP, alpha, intermediate, and full oxidation metabolites. Among these metabolites, backdiffusion of nonmetabolized BMIPP in blood significantly increased (27.9% +/- 7.7% to 42.3% +/- 8.1%; P < 0.05), especially in the early phase with ischemia. In tissue, the radioactivity was concentrated in the triglyceride pool even in the early phase, and in addition, BMIPP and alpha-oxidized metabolite significantly decreased in the early phase with ischemia (t = 1 min after BMIPP injection, 25.9% +/- 8.6% to 14.5% +/- 2.1%, P < 0.01; t = 2 min, 8.9% +/- 5.0% to 4.5% +/- 1.7%, P < 0.05).
These results show that backdiffusion of nonmetabolized BMIPP from the myocardium increased and BMIPP (long-chain fatty acids) in tissue decreased with ischemia, suggesting backdiffusion of nonmetabolized BMIPP might play an important role in myocardial perfusion-metabolism mismatch on SPECT images in patients with ischemic heart disease.
123I -（ρ - 碘苯基）-3 - R，S - 甲基十五烷酸（BMIPP）是一种用于单光子发射计算机断层显像（SPECT）成像的脂肪酸类似物。这种放射性药物具有独特的性质，即在缺血性心脏病患者的SPECT图像上存在灌注 - 代谢不匹配。然而，这种机制的原因仍不清楚。
在麻醉状态下使用开胸犬，我们构建了一个系统，必要时可将大冠状静脉的所有血液排出体外且不进行再循环。再灌注后左前降支动脉（LAD）闭塞30分钟。向LAD注射BMIPP后，从冠状静脉和腹主动脉取血样（6只犬）或从LAD区域取系列活检标本（5只犬），然后与正常对照进行比较。在流出研究中，使用高效液相色谱（HPLC）评估BMIPP的分解代谢产物，包括未代谢BMIPP的反向扩散。在组织分析研究中引入了薄层色谱（TLC）技术。
尽管BMIPP从血浆快速提取到心肌并随后滞留的情况未改变，但缺血时放射性的早期洗脱（8分钟）显著增加（从51%±12%增至65%±7%；P < 0.05）。心肌的代谢产物包括未代谢BMIPP的反向扩散、α、中间和完全氧化代谢产物。在这些代谢产物中，血液中未代谢BMIPP的反向扩散显著增加（从27.9%±7.7%增至42.3%±8.1%；P < 0.05），尤其是在缺血早期。在组织中，即使在早期放射性也集中在甘油三酯池中，此外，缺血早期BMIPP和α - 氧化代谢产物显著减少（BMIPP注射后1分钟，从25.9%±8.6%降至14.5%±2.1%，P < 0.01；2分钟时，从8.9%±5.0%降至4.5%±1.7%，P < 0.05）。
这些结果表明，缺血时未代谢BMIPP从心肌的反向扩散增加，组织中的BMIPP（长链脂肪酸）减少，提示未代谢BMIPP的反向扩散可能在缺血性心脏病患者SPECT图像上的心肌灌注 - 代谢不匹配中起重要作用。
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