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

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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.