Studies on radiopharmaceuticals with mitochondria membrane potential dependent tumor accumulation

点击翻译按钮获取中文摘要

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