研究者業績
基本情報
研究キーワード
2研究分野
1経歴
1-
2019年10月 - 現在
論文
85-
ChemMedChem 2024年6月7日In this study we developed a neopentyl 211At‐labeled activated ester that incorporates a triazole spacer and applied it to the synthesis of an 211At‐labeled cetuximab. The activated ester was synthesized via the nucleophilic 211At‐astatination of a neopentyl sulfonate carrying two long alkyl chains that serve as a lipid tag, which was followed by the hydrolysis of an acetal. Additionally, we developed a novel Resin‐Assisted Purification and Deprotection (RAPD) protocol involving a solid‐phase extraction of the protected 211At‐labeled compound from the mixture of the labeling reaction, hydrolysis of the acetal on the resin, and finally an elution of the 211At‐labeled activator from the resin. This method allows the synthesis of an 211At‐labeled activated ester with high purity through a simplified procedure that circumvents the need for HPLC purification. Using this 211At‐labeled activated ester, we efficiently synthesized 211At‐labeled cetuximab in 27±1% radiochemical yield with 95% radiochemical purity. This 211At‐activated ester demonstrated high reactivity, and enabled the completion of the reaction with the antibody within 10 min. In comparative biodistribution studies between 211At‐labeled cetuximab and the corresponding 125I‐labeled cetuximab in normal mice, both the thyroid and stomach showed radioactivity levels that were less than 1.0% of the injected dose.
-
Nuclear Medicine and Biology 132-133 108910 2024年5月 査読有り
-
Pharmaceuticals 2024年4月16日 査読有り
-
EJNMMI radiopharmacy and chemistry 9(1) 17-17 2024年2月26日BACKGROUND: L-type amino acid transporter 1 (LAT1) is overexpressed in various cancers; therefore, radiohalogen-labeled amino acid derivatives targeting LAT1 have emerged as promising candidates for cancer radiotheranostics. However, 211At-labeled amino acid derivatives exhibit instability against deastatination in vivo, making it challenging to use 211At for radiotherapy. In this study, radiohalogen-labeled amino acid derivatives with high dehalogenation stability were developed. RESULTS: We designed and synthesized new radiohalogen-labeled amino acid derivatives ([211At]At-NpGT, [125I]I-NpGT, and [18F]F-NpGT) in which L-tyrosine was introduced into the neopentyl glycol (NpG) structure. The radiolabeled amino acid derivatives were recognized as substrates of LAT1 in the in vitro studies using C6 glioma cells. In a biodistribution study using C6 glioma-bearing mice, these agents exhibited high stability against in vivo dehalogenation and similar biodistributions. The similarity of [211At]At-NpGT and [18F]F-NpGT indicated that these pairs of radiolabeled compounds would be helpful in radiotheranostics. Moreover, [211At]At-NpGT exhibited a dose-dependent inhibitory effect on the growth of C6 glioma-bearing mice. CONCLUSIONS: [211At]At-NpGT exhibited a dose-dependent inhibitory effect on the tumor growth of glioma-bearing mice, and its biodistribution was similar to that of other radiohalogen-labeled amino acid derivatives. These findings suggest that radiotheranostics using [18F]F-NpGT and [123/131I]I-NpGT for diagnostic applications and [211At]At-NpGT and [131I]I-NpGT for therapeutic applications are promising.
MISC
7-
JOURNAL OF NUCLEAR MEDICINE 44(5) 305P-305P 2003年5月
-
Biomedical research on trace elements 12(2) 152-158 2001年
-
JOURNAL OF NUCLEAR MEDICINE 41(5) 228P-229P 2000年5月
-
NUCLEAR MEDICINE AND BIOLOGY 26(8) 883-890 1999年11月Recent development of a variety of thiol free chelating agents has facilitated the design of Tc-99m-labered somatostatin analogs suitable for receptor imaging of somatostatin-positive tumors. However, it remains ambiguous whether the disulfide bonds in cyclic peptides are stable during Tc-99m complexation reactions, and contradictory results have been reported regarding the integrity of disulfide bonds in cyclic somatostatin analogs. To estimate the stability of the disulfide bond in a synthetic somatostatin analog at low peptide concentrations, [I-125]I-RC 160, in which radioiodine was incorporated into the 3-Tyr residue, was synthesized and the integrity of the disulfide bond of the peptide was investigated in the presence of reducing agents such as ascorbic acid, dithionite, and stannous ions. The disulfide bond in [I-125]I-RC-160 remained stable in the presence of ascorbic acid in boiling water. The disulfide bond was also stable when treated with stannous ions at concentrations sufficient to reduce Tc-99m for complexation with a thiol free chelating agent, bis(hydroxamamide) analog when the Tc-99m complexation reaction was performed at room temperature. However, the disulfide bond of [I-125]I-RC-160 was slightly cleaved in the presence of a small amount of stannous ions when the reaction was performed in boiling water. Treatment of [I-125]I-RC-160 with dithionite in boiling water markedly reduced the disulfide bond of the parental peptide. These findings indicated that synthetic somatostatin analogs may be labeled with Tc-99m with stannous ions as the reducing agent without impairing their structure after conjugation of thiol free chelating agents that provide Tc-99m chelates under mild reaction conditions. (C) 2000 Elsevier Science Tnc, All rights reserved.
講演・口頭発表等
4-
核医学診断・治療のためのRI利用シンポジウムー64Cu・67Cu：核種構造と治療薬剤創製の展望ー 2021年5月20日
所属学協会
3共同研究・競争的資金等の研究課題
31-
日本学術振興会 科学研究費助成事業 2022年4月 - 2027年3月
-
日本学術振興会 科学研究費助成事業 2023年4月 - 2026年3月
-
日本学術振興会 科学研究費助成事業 2022年4月 - 2025年3月
-
日本学術振興会 科学研究費助成事業 2022年4月 - 2025年3月
-
日本学術振興会 科学研究費助成事業 2020年4月 - 2023年3月