Presentation Development of quantum scientific/therapeutic tool: Synthesis and therapeutic effect of At-211 labeled probe for melanoma with overexpressed metabotropic glutamate receptor 1

Hanyu, Masayuki  ,  Fujinaga, Masayuki  ,  Xie, Lin  ,  Zhang, Yiding  ,  Morokoshi, Yukie  ,  Keiko Li, Huizi  ,  Minegishi, Katsuyuki  ,  Hasegawa, Sumitaka  ,  Nagatsu, Kotaro  ,  Ming-Rong, Zhang

Metabotropic glutamate receptor 1 (mGluR1) is found ectopically in various kinds of cancers, such as melanoma and breast cancer. It has been reported that overexpressed mGluR1 exhibited oncogenic characteristics that independently trigger melanocyte tumorigenesis. Further, inhibition or inactivation of mGlu1 was demonstrated to prevent growth and progression of melanomas. Recently, we developed 4-[18F]fluoro-N-[4-(6-(isopropylamino)pyrimidin-4-yl)-1,3-thiazol-2-yl]-N-methylbenzamide ([18F]FITM) and its other halogen-substituted analogs as PET probes for in vivo imaging of mGluR1 in melanoma. In this study, we synthesized 4-[211At]astato-N-[4-(6-(isopropylamino)pyrimidin-4-yl)-1,3-thiazol-2-yl]-N-methylbenzamide ([211At]1) and evaluated their antitumoral effects on mice bearing B16F10 melanoma. 211At was produced using a remotely controlled versatile system developed in house. Synthesis of [211At]1 was performed by reaction of tin precursor with 211At (74~222 MBq in 2%AcOH/MeOH) in the presence of N-chlorosccinimide (1 mg/mL) at room temperature for 20 min. After purification and formulation, [211At]1 was obtained in 25.7±7.8 % radiochemical yield and radiochemical purity of [211At]1 was >99% at the end of synthesis (n=3, based on the total 211At). Treatment the B16F10-bearing mice with [211At]1 at 1.85 MBq in 1 doses/mouse significantly reduced the tumor volumes (P < 0.05).
QST第1回国際シンポジウム『量子生命科学 -Quantum Life Science-』

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