In Vivo Nitroreductase Imaging via Fluorescence and Chemical Shift Dependent ¹⁹ F NMR

Nitroreductase (NTR) is an important biomarker widely used to evaluate the degree of tumor hypoxia. Although a few optical methods have been reported for detecting nitroreductase at low concentration ranges, an effective strategy for nitroreductase monitoring in vivo without limits to the imaging depth is still lacking. Herein, a novel dual-mode NIR fluorescence and ¹⁹ F MRI agent, FCy7-NO₂ , is proposed for imaging tumor hypoxia. We show that FCy7-NO₂ serves as not only a rapid NIR fluorescence enhanced probe for monitoring and bioimaging of nitroreductase in tumors, but also a novel ¹⁹ F MR chemical shift-sensitive contrast agent for selectively detecting nitroreductase catalyzed reduction. Notably, integrating two complementary imaging technologies into FCy7-NO₂ enables sensitive detection of nitroreductase in a broad concentration range without tissue-depth limit. In general, this agent has a remarkable response to nitroreductase, which provides a promising method for understanding tumor evolution and its physiological role in the hypoxic microenvironment.