It has been reported that
sigma receptors are highly expressed in a variety of human
tumors. In this study, we selected (+)-2-[4-(4-iodophenyl)piperidino]
cyclohexanol [(+)-pIV] as a
sigma receptor ligand and evaluated the potential of radioiodinated (+)-pIV for
tumor imaging and
therapy. (+)-[(125/131)I]pIV was prepared by an iododestannylation reaction under no-carrier-added conditions with radiochemical purity over 99% after HPLC purification. Biodistribution experiments were performed by the
intravenous injection of (+)-[(125)I]pIV into mice bearing human prostate
tumors (DU-145). Blocking studies were performed by
intravenous injection of (+)-[(125)I]pIV mixed with an excess amount of unlabeled sigma
ligand into DU-145
tumor-bearing mice. For therapeutic study, (+)-[(131)I]pIV was injected at a dose of 7.4 MBq followed by measurement of the
tumor size. In biodistribution experiments, (+)-[(125)I]pIV showed high uptake and long residence in the
tumor. High
tumor to blood and muscle ratios were achieved because the radioactivity levels of blood and muscle were low. However, the accumulations of radioactivity in non-target tissues, such as liver and kidney, were high. The radioactivity in the non-target tissues slowly decreased over time. Co-injection of (+)-[(125)I]pIV with an excess amount of unlabeled sigma
ligand resulted in a significant decrease in the
tumor/blood ratio, indicating
sigma receptor-mediated
tumor uptake. In therapeutic study,
tumor growth in mice treated with (+)-[(131)I]pIV was significantly inhibited compared to that of an untreated group. These results indicate that radioiodinated (+)-pIV has a high potential for
sigma receptor imaging in
tumor and
radionuclide receptor
therapy.