@misc{oai:repo.qst.go.jp:00072766,
 author = {大島, 康宏 and 渡辺, 茂樹 and 坂下, 哲哉 and 佐々木, 一郎 and 東, 達也 and 石岡, 典子 and 大島 康宏 and 渡辺 茂樹 and 坂下 哲哉 and 佐々木 一郎 and 東 達也 and 石岡 典子},
 month = {Apr},
 note = {Background / Aims: We have developed meta-[211At]astato-benzylguanidine (MABG) for targeted alpha-radionuclide therapy of malignant pheochromocytoma and shown its high antitumor effects in tumor-bearing mice. However, body weight loss, an indicator of toxicity, was transiently observed at therapeutic dose. In this study, we investigated for alleviation of toxicity whether non-specific uptake of MABG could be reduced by inhibiting organic cation transporter (OCT). 
Methods: The uptake of MABG was examined using the following cell lines, PC-12, rat pheochromocytoma, HT-29, human colorectal adenocarcinoma, ACHN, human renal cell adenocarcinoma, BxPC-3, human pancreatic adenocarcinoma. To inhibit OCT, cells were treated with phenoxybenzamine (POB), an inhibitor of OCT1-3, ranitidine (RAN), an inhibitor of OCT1, or hydrocortisone (HDC), an inhibitor of OCT3. 
Results: POB (3 μM), RAN (100 μM) and HDC (10 μM) significantly reduced the uptake of MABG in HT-29, ACHN and BxPC-3. While, the uptake of MABG in PC-12 was slightly inhibited by treatment with POB, but not RAN and HDC. These results indicate that OCT1 and OCT3 were involved in the uptake of MABG in HT-29, ACHN and BxPC-3, but not in PC-12. Therefore, RAN or HDC possibly inhibit the non-specific uptake of MABG in colon, kidney and pancreas. Dose-response study showed that the inhibitory effect of RAN and HDC in HT-29, ACHN and BxPC-3 was enhanced dose-dependently. However, high-dose of RAN (1000 μM), but not HDC (100 μM), reduced the uptake of MABG in PC-12. These results suggest that HDC can inhibit the nonspecific uptake of MABG more selectively.
Conclusion: Our results showed that the non-specific uptake of MABG is possibly reduced by inhibiting OCT1 and OCT3. Furthermore, HDC is a clinically approved drug, and can be a selective inhibitor for reducing non-specific uptake of MABG. At present, we are investigating the usefulness of HDC in tumor-bearing mice., 12th World Congress of The World Federation of Nuclear Medicine and Biology (WFNMB2018)},
 title = {Inhibition of organic cation transporter reduces non-specific uptake of MABG},
 year = {2018}
}