Ultra-Radiostable Covalent Conformationally Interlocked Networks Enabling a Universal Radiometal-Labeling Platform for Cancer Radioembolization.

Authors

Xiao Xu, Zhenwen Zhao, Yangjie Wang, Zhigang Liu, Zhijie Liu, Xiaoling Li, Zhichen Mao, Lu Xu, Gan Lin, Gang Liu, Hongjuan Ma

Published in

Advanced science (Weinheim, Baden-Wurttemberg, Germany). Pages e76278. Jun 23, 2026. Epub Jun 23, 2026.

Abstract

Transcatheter arterial embolization (TARE) has emerged as a highly effective locoregional treatment for advanced liver cancer, which represents a significant advancement in clinical practice. Nonetheless, the utilization of traditional radioactive microspheres in TARE is hindered by various material and technical challenges that necessitate resolution. Herein, we present, for the first time, well-designed and synthesized conjugated poly(imide dioxime) ligand-based microspheres (PID-Ms) with a remarkable radiometal coordinate covalent conformational interlocked network. PID-Ms can be radiolabeled with various radionuclides, including ¹⁷⁷Lu, ⁹⁰Y, ¹⁸⁸Re, ⁶⁸Ga, and ^99mTc, can be achieved at low temperatures (40°C), and for diagnostic imaging and radiotherapy applications. The combined strategy of extended x-ray absorption fine structure spectroscopy (EXAFS), DFT calculations, and in vitro and in vivo radiostability experiments collectively confirmed that radiometal-PID complexes exhibit ultra-high radiostability. ¹⁷⁷Lu-PID-Ms were employed to accurately predict normal organ shunts and radiotherapy in rat and rabbit VX2 orthotopic live tumor models, demonstrating their ultra-radiostability and remarkable anti-tumor efficacy. Furthermore, Radiometals-PID-Ms have an adjustable shelf life, enabling on-demand radiolabeling for drug preparation, achieving rapid 'on-demand' capability. This innovative approach has the potential to inspire the synthesis of numerous coordination polymeric materials for various applications in PET/SPECT-mediated radiopharmaceutical therapy, alpha-nucleophile-targeted radiotherapy, and MRI contrast agents.

PMID:
42335402
Bibliographic data and abstract were imported from PubMed on 24 Jun 2026.

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