基于硼酸酯的19F磁共振分子探针的设计合成及活体深组织活性氧物种的激活响应成像

活性氧簇(ROS), 如过氧化氢, 在生物体内的各种生理和病理过程中发挥着重要作用. 生物体内活性氧簇水平的异常与多种疾病(炎症、 肿瘤和器官损伤等)密切相关, 使ROS监测成为研究和诊断这些疾病的重要工具. 目前, 实现活体内深组织中的活性氧簇成像仍然面临挑战. 本文设计并合成了一种响应型的¹⁹F磁共振成像(MRI)探针(Gd-DPBF), 并将其用于实现对活体内通用活性氧簇的检测和成像. 该探针由钆螯合物通过活性氧簇响应的芳香硼酸酯键与含氟砌块相连接构成. 体外和体内成像实验结果证实, 该探针可以实现在活体荷瘤小鼠中针对肿瘤中高表达的活性氧进行检测和成像, 展示了其在生物体内对活性氧簇相关生理过程进行深组织、 零生物背景成像方面的潜力.

Boronate-based 19F NMR/MRI Molecular Probe for Activatable Deep-tissue Imaging of Reactive Oxygen Species

Reactive oxygen species（ROS）， such as hydrogen peroxide， are playing critical roles in various physiological and pathological processes of organisms. There is a close correlation between abnormal levels of ROS and disease conditions including inflammation， tumor， and organ injuries， which renders ROS detection attractive as an important tool for the research and diagnosis of these diseases. However， imaging ROS in deep tissues of living subjects remains challenging. In this paper， we report the development of an activatable ¹⁹F magnetic resonance imaging（MRI） probe（Gd-DPBF） for sensing and imaging of generic ROS in living mice. Gd-DPBF is composed of a gadolinium chelate and a fluorinated moiety via a ROS-responsive aromatic boronate linkage. The capacity of Gd-DPBF for visualizing generic ROS in deep tissues and in the tumors of living mice is validated by a series of ex vivo and in vivo imaging experiments， illustrating its promising potential for in-depth and background-free imaging of various ROS-related biological processes in living subjects.