Glycerol-weighted chemical exchange saturation transfer nanoprobes allow FH dual-modality magnetic resonance imaging-guided cancer radiotherapy.

Recently, radiotherapy (RT) has entered a new realm of precision cancer therapy with the introduction of magnetic resonance (MR) imaging guided radiotherapy systems into the clinic. Nonetheless, identifying an optimized radiotherapy time window (ORTW) is still critical for the best therapeutic efficacy of RT. Here we describe pH and O dual-sensitive, perfluorooctylbromide (PFOB)-based and glycerol-weighted chemical exchange saturation transfer (CEST) nano-molecular imaging probes (Gly-PFOBs) with dual fluorine and hydrogen proton based CEST MR imaging properties (F/H-CEST). Oxygenated Gly-PFOBs ameliorate tumor hypoxia and improve O-dependent radiotherapy. Moreover, the pH and O dual-sensitive properties of Gly-PFOBs could be quantitatively, spatially, and temporally monitored by F/H-CEST imaging to optimize ORTW. In this study, we describe the CEST signal characteristics exhibited by the glycerol components of Gly-PFOBs. The pH and O dual-sensitive Gly-PFOBs withF/H-CEST MR dual-modality imaging properties, with superior therapeutic efficacy and biosafety, are employed for sensitive imaging-guided lung cancer RT, illustrating the potential of multi-functional imaging to noninvasively monitor and enhance RT-integrated effectiveness.