Ode Yudai, Pradipta Ambara R, Ahmadi Peni, Ishiwata Akihiro, Nakamura Akiko, Egawa Yasuko, Kusakari Yuriko, Muguruma Kyohei, Wang Yang, Yin Xiaojie, Sato Nozomi, Haba Hiromitsu, Tanaka Katsunori
Department of Chemical Science and Engineering, School of Materials and Chemical Technology, Tokyo Institute of Technology 2-12-1 Ookayama Meguro Tokyo 152-8552 Japan
Biofunctional Synthetic Chemistry Laboratory, Cluster for Pioneering Research, RIKEN 2-1 Hirosawa, Wako Saitama 351-0198 Japan.
Chem Sci. 2023 Jun 27;14(30):8054-8060. doi: 10.1039/d3sc02513f. eCollection 2023 Aug 2.
Targeted α-particle therapy (TAT) is an attractive alternative to conventional therapy for cancer treatment. Among the available radionuclides considered for TAT, astatine-211 (At) attached to a cancer-targeting molecule appears very promising. Previously, we demonstrated that aryl azide derivatives could react selectively with the endogenous acrolein generated by cancer cells to give a diazo compound, which subsequently forms a covalent bond with the organelle of cancer cells . Herein, we synthesized At-radiolabeled 2,6-diisopropylphenyl azide (ADIPA), an α-emitting molecule that can selectively target the acrolein of cancer cells, and investigated its antitumor effect. Our results demonstrate that a single intratumor or intravenous administration of this simple α-emitting molecule to the A549 (human lung cancer) cell-bearing xenograft mouse model, at a low dose (70 kBq), could suppress tumor growth without inducing adverse effects. Furthermore, because acrolein is generally overproduced by most cancer cells, we believe ADIPA is a simple TAT compound that deserves further investigation for application in animal models and humans with various cancer types and stages.
靶向α粒子疗法（TAT）是癌症治疗中传统疗法的一种有吸引力的替代方法。在考虑用于TAT的现有放射性核素中，附着于癌症靶向分子的砹-211（At）显得非常有前景。此前，我们证明芳基叠氮衍生物可与癌细胞产生的内源性丙烯醛选择性反应生成重氮化合物，该重氮化合物随后与癌细胞的细胞器形成共价键。在此，我们合成了At放射性标记的2,6-二异丙基苯基叠氮（ADIPA），一种可选择性靶向癌细胞丙烯醛的α发射分子，并研究了其抗肿瘤作用。我们的结果表明，以低剂量（70 kBq）向携带A549（人肺癌）细胞的异种移植小鼠模型单次瘤内或静脉注射这种简单的α发射分子，可抑制肿瘤生长而不产生不良反应。此外，由于大多数癌细胞通常会过量产生丙烯醛，我们认为ADIPA是一种简单的TAT化合物，值得在各种癌症类型和阶段的动物模型和人类中进一步研究其应用。
