Issue 30, 2023

Therapeutic efficacy of 211At-radiolabeled 2,6-diisopropylphenyl azide in mouse models of human lung cancer

Abstract

Targeted α-particle therapy (TAT) is an attractive alternative to conventional therapy for cancer treatment. Among the available radionuclides considered for TAT, astatine-211 (211At) 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 in vivo. Herein, we synthesized 211At-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.

Graphical abstract: Therapeutic efficacy of 211At-radiolabeled 2,6-diisopropylphenyl azide in mouse models of human lung cancer

Supplementary files

Article information

Article type
Edge Article
Submitted
18 may 2023
Accepted
26 may 2023
First published
27 iyn 2023
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2023,14, 8054-8060

Therapeutic efficacy of 211At-radiolabeled 2,6-diisopropylphenyl azide in mouse models of human lung cancer

Y. Ode, A. R. Pradipta, P. Ahmadi, A. Ishiwata, A. Nakamura, Y. Egawa, Y. Kusakari, K. Muguruma, Y. Wang, X. Yin, N. Sato, H. Haba and K. Tanaka, Chem. Sci., 2023, 14, 8054 DOI: 10.1039/D3SC02513F

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