Development of a radioiodinated lipophilic cation as a new SPECT radiopharmaceutical for cancer diagnosis.

线粒体在癌细胞表型中的作用与细胞氧化还原平衡、细胞周期进程、质子梯度的变化有关，因此，癌细胞和正常细胞之间的线粒体膜电位存在很大差异。这种线粒体膜电位差的开发导致选择亲脂性阳离子化合物作为肿瘤成像剂，通过预期由于电化学质子梯度在肿瘤细胞中带负电荷的线粒体中的选择性积累。在这项研究中，我们合成了一种放射性碘标记的罗丹菁染料，MKT 077衍生物（IBMKT），一种n电子离域亲脂性阳离子，并评估其用于癌症诊断的潜力。通过<125>卤素交换反应合成了[^ I]IBMKT，HPLC纯化后总放射化学产率为50%。产物的放射化学纯度大于95%，并且所产生的[^<125>I]IBMKT在标记后至少稳定一个月。通过测定六种癌细胞系对IBMKT的摄取来研究向肿瘤细胞中的选择性积累。在与肿瘤细胞一起孵育时，[^<125>I]IBMKT在肿瘤细胞中的蓄积量比在正常细胞中的蓄积量大得多，与正常细胞相比，肿瘤细胞中的蓄积量是正常细胞的2- 7倍。此外，使用放射性标记的Rb测定这些肿瘤细胞的线粒体膜电位，并与细胞的[^<125>I]IBMKT积累进行比较。因此，肿瘤细胞积累的[^<125>I]IBMKT与这些细胞的线粒体膜电位密切相关。此外，荷瘤小鼠的生物分布研究表明，[^<125>I]IBMKT在肿瘤中的蓄积高于血液和肌肉中的蓄积。这些结果表明，这种新设计的放射性碘标记的IBMKT似乎持有肿瘤显像的SPECT研究的潜力。

The role of mitochondria in cancer cell phenotypes has been related with changes in cellular redox balance, cell cycle progression, protons gradients thus, large differences in mitochondrial membrane potential between carcinoma cells and normal cells occurs. Exploitation of this mitochondrial membrane potential difference has lead to the selection of a lipophilic cationic compound as a tumor-imaging agent by expecting the selective accumulation in negatively charged mitochondria in tumor cells due to the electrochemical proton gradient. In this study, we synthesized a radioiodinated rhodacyanine dye, MKT 077 derivative (IBMKT), a n electron-delocalized lipophilic cation, and evaluated its potential for cancer diagnosis.[^<125>I]IBMKT was synthesized by a halogen-exchange reaction with the total radiochemical yield of 50% after HPLC purification. The radiochemical purity of the product was greater than 95%, and the produced [^<125>I]IBMKT was stable for at least one month after labeling. The selective accumulation into tumor cells was investigated by determining the uptake of IBMKT by six cancer cell lines. In incubation with tumor cells, [^<125>I]IBMKT was accumulated by tumor cells to a much, greater than by normal cells it accumulated 2-to 7-fold by tumor cells, as compared with that by normal cells. Furthermore, the mitochondrial membrane potential of these tumor cells was determined using radiolabeled, Rb and compared with the accumulation of [^<125>I]IBMKT by the cells. Consequently, the accumulation of [^<125>I]IBMKT by the tumor cells correlated well with the mitochondrial membrane potential of these cells. In addition, biodistribution studies in tumor-bearing mice showed higher accumulation of [^<125>I]IBMKT in tumor than those in the blood and muscle. These results indicate that this newly designed radioiodinated IBMKT seemed to hold potential for the SPECT study of tumor imaging.