Activatable near-infrared fluorescence and chemical exchange saturation transfer MRI multimodal imaging probe for tumor detection in vitro and in vivo.

Multimodal imaging has emerged as a powerful tool in biomedical research and clinical diagnostics. Ideally, it combines multiple imaging techniques to provide complementary anatomical and molecular information in living subjects. Particularly desirable are multimodal imaging probes capable of providing differential diagnostic signals upon interaction with specific molecular targets. Hydrogen peroxide (HO) is a key target in this regard, since it is typically overexpressed in cancer cells. In this study, we present a small-molecule probe that not only selectively detects endogenous HO through multimodal imaging, with a significant HO-triggered 15-fold fluorescence enhancement but also turns "on" a chemical exchange saturation transfer (CEST) magnetic resonance (MR) response with 60-fold signal enhancement at pH 7.4. Excellent selectivity against various other biologically relevant species is seen. Using this probe, we observed 3.4-4.5-fold and 2.8-5.8-fold higher HO levels in cancerous cell lines and tumor tissues compared to normal cell lines and tissues, respectively. Time-dependent in vivo fluorescence and CEST imaging in a HeLa (Henrietta Lacks) tumor xenograft mouse model revealed probe-dependent tumor detection by fluorescence and CEST MRI contrast in the tumor area. These observations are attributed to the relatively high endogenous HO levels produced during mitosis. This newly developed probe holds promise for advancing our understanding of HO-related biology and for cancer detection both in vitro and in vivo.