放射性核種を置き換えるだけで「診る」と「治す」ができる薬剤を開発 ～悪性黒色腫など幅広いがん種に対する強力かつ安全な個別化医療として期待～

2026-03-11 量子科学技術研究開発機構

​図１　マウス由来悪性黒色腫の培養細胞を用いた¹¹C-IMTMと²¹¹At-AMTMの結合性評価
mGluR1阻害薬を添加した場合に結合性が有意に低下していることから、どちらの薬剤もmGluR1に特異的に結合していることが確認できました。

＜関連情報＞

• https://www.qst.go.jp/site/press/20260311-2.html
• https://www.cell.com/molecular-therapy-family/molecular-therapy/abstract/S1525-0016(26)00118-8

mGluR1を標的とした放射線治療戦略は、メラノーマと膵臓癌の病変を可視化し、抗腫瘍効果を増強する A mGluR1-targeted radiotheranostic strategy visualizes lesions and potentiates antitumor efficacy in melanoma and pancreatic cancer

Lin Xie ∙ Masayuki Hanyu ∙ Masayuki Fujinaga ∙ … ∙ Nobuki Nengaki ∙ Kotaro Nagatsu ∙ Ming-Rong Zhang
Molecular therapy  Published:March 10, 2026
DOI:https://doi.org/10.1016/j.ymthe.2026.02.032

Abstract

Targeting metabotropic glutamate receptor 1 (mGluR1), an oncoprotein involved in glutamine metabolism that is frequently overexpressed in most cancers, is a promising strategy for cancer treatment and management. Here, we engineered a radiotheranostic strategy to target mGluR1 by integrating positron emission tomography (PET)-guided targeted α-particle therapy (TAT) with a small-molecule pair, β⁺-emitting ¹¹C-IMTM and α-emitting ²¹¹At-AMTM, to identify and eradicate refractory cancers, including melanoma and pancreatic cancer. ¹¹C-IMTM PET clearly visualized the primary and metastatic melanoma burden; α-particles from ²¹¹At-AMTM anchored to mGluR1 downregulated this oncoprotein, which was subsequently internalized to trigger cancer cell senescence via the p21/caveolin-1 pathway. In mice with localized and metastatic melanoma, a single dose of ²¹¹At-AMTM induced a >86% reduction in tumor volume and a 2-fold increase in survival. Moreover, 46.67% (7/15) of the tumor-bearing mice exhibited complete elimination of pancreatic cancer without significant toxicity. This mGluR1-targeted radiotheranostic strategy, ¹¹C-IMTM PET-guided ²¹¹At-AMTM TAT, represents an effective approach for the diagnosis and treatment of melanoma and pancreatic cancer and provides unique insights into the clinical development and application of approaches targeting cancer-specific metabolic vulnerabilities.