Studies on radiopharmaceuticals with mitochondria membrane potential dependent tumor accumulation

众所周知，亲脂性阳离子放射性药物如T1-201或Tc-99 m-MIBI（MIBI）在某些肿瘤中蓄积，并且它们可用于肿瘤诊断。T1-201和MIBI目前都用于心肌血流显像。据报道，这两种放射性药物在心肌细胞中的摄取机制和动力学不同。根据这些报道，细胞中的MIBI几乎存在于线粒体部分中，并且心肌细胞对MIBI的摄取依赖于线粒体膜电位。实际上，心肌的膜电位高于其他器官的膜电位。此外，部分肿瘤细胞的线粒体膜电位高于正常细胞--预计MIBI在肿瘤细胞中的蓄积依赖于膜电位。在此基础上，利用体外细胞培养技术，对肿瘤细胞对阳离子放射性药物的摄取动力学和病理生理学进行了研究。 ...更多信息 本研究的实验体系：首先，我们制备了体外实验用的肿瘤细胞株。用JC-1测定了这些细胞的相对线粒体膜电位，结果表明膜电位变化很大。在体外实验中，观察到肿瘤细胞的膜电位和MIBI摄取之间的高度相关性。此外，在FDG的情况下也显示出类似的关系。由于线粒体膜电位与能量代谢活动有关，因此，上述结果表明，摄取这两种化合物可作为肿瘤细胞活性的指标。其次，我们进行了光动力疗法（PDT）后肿瘤细胞摄取MIBI和FDG的研究。在PDT照射后1-3小时，仅在MIBI摄取中观察到每个细胞约50%的减少。这一现象可能是光动力诱导细胞凋亡引起线粒体功能改变的结果。MIBI和FDG摄取之间的这种差异使我们对治疗后肿瘤细胞状况的诊断感兴趣。少

It is well known that lipophilic cation radiopharmaceuticals such as T1-201 or Tc-99m-MIBI (MIBI) accumulate in some tumors and they are useful for tumor diagnosis. Both T1-201 and MIBI are currently used for myocardial blood flow scintigraphy. The uptake mechanism and kinetics in myocaridium cells have been reported to be different in these two radiopharmaceuticals. According to these reports, almost MIBI in the cells exist in the mitochondria fraction and the uptake of MIBI by myocardium cells depends on mitochondria membrane potential. Actually, the membrane potential of the myocardium is higher than that of other organs. In addition, the mitochondria membrane potential of some tumor cells is higher than that of normal cells_ It is expected that MIBI accumulates in the tumor cells depending on the membrane potential. On these basis, the uptake kinetics and patho-physiological studies of such cationic radiopharmaceuticals in the tumor cells was evaluated using in vitro cell culture e … More xperimental system in this research.First of all, we prepared some tumor cell lines for in vitro experiments. Relative mitochondria membrane potential of these cells was evaluated with JC-1 and a large variation of the membrane potential was indicated. In in vitro experiments, a high relationship between the membrane potential and MIBI uptake in the tumor cells was observed. In addition, similar relationship was shown in case of FDG. Because mitochondria membrane potential relates to the activity of energy metabolism, these results suggested that the uptake of both compounds can be used as index of the tumor cells activity. Next, we perforthed MIBI and FDG uptake studies in the tumor cells after photo dynamic therapy (PDT). About 50 % decrease per cell at 1-3 hours post PDT irradiation was observed in only MIBI uptake. It is suggested this phenomenon is derived from the alteration of mitochondria function because of apoptosis induced by PDT. This discrepancy between MIBI and FDG uptake interests us for diagnosis of tumor cell condition after therapy. Less