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用于监测酸性条件下金属-有机框架内质子转移的辐射发光金属-有机框架

A Radioluminescent Metal-Organic Framework for Monitoring Ac .

机构信息

State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China.

Key Laboratory of Radiation Physics and Technology of the Ministry of Education Institute of Nuclear Science and Technology, Sichuan University, Chengdu 610064, China.

出版信息

J Am Chem Soc. 2023 Jul 12;145(27):14679-14685. doi: 10.1021/jacs.3c02325. Epub 2023 Jun 27.

Abstract

Ac is considered as one of the most promising radioisotopes for alpha-therapy because its emitted high-energy α-particles can efficiently damage tumor cells. However, it also represents a significant threat to healthy tissues owing to extremely high radiotoxicity if targeted therapy fails. This calls for a pressing requirement of monitoring the biodistribution of Ac during the treatment of tumors. However, the lack of imageable photons or positrons from therapeutic doses of Ac makes this task currently quite challenging. We report here a nanoscale luminescent europium-organic framework (EuMOF) that allows for fast, simple, and efficient labeling of Ac in its crystal structure with sufficient Ac-retention stability based on similar coordination behaviors between Ac and Eu. After labeling, the short distance between Ac and Eu in the structure leads to exceedingly efficient energy transduction fromAc-emitted α-particles to surrounding Eu ions, which emits red luminescence through a scintillation process and produces sufficient photons for clearcut imaging. The intensity distribution of radioluminescence signal originating from the Ac-labeled EuMOF is consistent with the dose of Ac dispersed among the various organs determined by the radioanalytical measurement , certifying the feasibility of directly monitoring Ac using optical imaging for the first time. In addition, Ac-labeled EuMOF displays notable efficiency in treating the tumor. These results provide a general design principle for fabricating Ac-labeled radiopharmaceuticals with imaging photons and propose a simple way to track radionuclides with no imaging photons, including but not limited to Ac.

摘要

锕(Ac)被认为是最有前途的放射性同位素之一,可用于α-治疗,因为其发射的高能α粒子可以有效地破坏肿瘤细胞。然而,如果靶向治疗失败,由于极高的放射性毒性,它也对健康组织构成了重大威胁。这就迫切需要在肿瘤治疗过程中监测 Ac 的生物分布。然而,由于治疗剂量的 Ac 缺乏可成像的光子或正电子,使得这项任务目前极具挑战性。我们在这里报告了一种纳米级发光的铕-有机骨架(EuMOF),它允许基于 Ac 和 Eu 之间相似的配位行为,在 Ac 的晶体结构中快速、简单且有效地进行标记,并且具有足够的 Ac 保留稳定性。标记后,结构中 Ac 和 Eu 之间的短距离导致 Ac 发射的α粒子向周围 Eu 离子极其有效地能量转移,通过闪烁过程发出红色荧光,并产生足够的光子进行清晰的成像。源自 Ac 标记的 EuMOF 的放射发光信号的强度分布与通过放射性分析测量确定的分布在各个器官中的 Ac 剂量一致,这首次证明了使用光学成像是可行的,可直接监测 Ac。此外,Ac 标记的 EuMOF 在治疗肿瘤方面表现出显著的效率。这些结果为制造带有成像光子的 Ac 标记放射性药物提供了通用的设计原则,并提出了一种简单的方法来追踪没有成像光子的放射性核素,包括但不限于 Ac。

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