@misc{oai:repo.qst.go.jp:00072760,
 author = {Hanyu, Masayuki and Xie, Lin and Fujinaga, Masayuki and Zhang, Yiding and Hatori, Akiko and Morokoshi, Yukie and Li, Huizi and Minegishi, Katsuyuki and Hasegawa, Sumitaka and Nagatsu, Kotaro and Zhang, Ming-Rong and 破入 正行 and 謝 琳 and 藤永 雅之 and 張 一鼎 and 羽鳥 晶子 and 諸越 幸恵 and 李 惠子 and 峯岸 克行 and 長谷川 純崇 and 永津 弘太郎 and 張 明栄},
 month = {Apr},
 note = {Background / Aims: Ectopically expressed metabotropic glutamate receptor 1 (mGluR1) independently induces melanocyte carcinogenesis [1], and it is therefore becoming an important target for personalized diagnosis and treatment strategies for melanomas [2,3]. Recently, we developed [18F]FITM and its other radiohalogen-substituted probes for PET imaging of mGluR1 in melanoma [3,4]. In this study, we synthesized 4-[131I]iodo ([131I]1)- or 4-[211At]astato ([211At]1)- N-[4-(6-(isopropylamino)pyrimidin-4-yl)-1,3-thiazol-2-yl]-N-methylbenzamide as two target-radionuclide-therapy probes and  evaluated their antitumor effects on mice bearing B16F10 melanoma. 
Methods: Unlabeled 1 and its tin precursor for radiosynthesis were prepared according to the method reported by our laboratory [2,3]. Radiosynthesis of [131I]1 was performed by reaction of tin precursor with [131I]NaI in the presence of 30% H2O2 at room temperature for 2 h. 211At for radiolabeling was produced using a remotely controlled versatile system developed in house [5]. The anti-tumor effect of two radioprobes was evaluated in the mice bearing B16F10 melanoma with rich mGluR1 expression. Animal studies were approved by the Animal Ethics Committee of the National Institutes for Quantum and Radiological Science and Technology.
\nResults: After purification and formulation, [131I]1 was obtained in 45 ± 20% radiochemical yield (n > 3, based on the total [131I]NaI). The molar radioactivity and radiochemical purity of [131I]1 were 40 ± 4 GBq/μmol and >99%. [211At]1 was successfully synthesized by the reaction of tin precursor with 211At in the presence of N-chlorosuccinimide at room temperature for 1 h. The radiochemical conversion of [211At]1 exceeded 40%. Treatment the B16F10-bearing mice with [131I]1 at 18 MBq and 9 MBq in 2 doses/mouse reduced the tumor volumes (P < 0.05), compared to the untreated group. Further, the administration of [211At]1 at 1.1 MBq in single doses/mouse significantly inhibited B16F10-melanoma growth, resulted in tumor regression and a durable anti-tumor response.
\nConclusions: [131I]1 and [211At]1 are useful radioprobes for targeted radiotherapy of melanoma with overexpressed mGluR1. 
\nReferences: [1]. Pollock PM, et al. Nat Genet, 2003, 34,108-112. [2] L. Xie, et al. Int J Cancer, 2014, 135, 1852-59. [3] M. Fujinaga, et al. J Med Chem, 2015, 58, 1513-23. [4] M. Fujinaga, et al. J Med Chem, 2012, 55, 11042-51. [5] K. Nagatsu, et al. Appl Radiat Isot, 2014, 94, 363-71., 12th Congress of the World federation of Nuclear Medicine and Biology},
 title = {Development and radiotherapeutic effect of two novel I-131 or At-211 labelled radioprobes for melanoma with overexpressed metabotropic glutamate receptor 1},
 year = {2018}
}