An Integrated Afterglow and MRI Probe for In Vivo Imaging of ATP in Tumor Metabolism

Adenosine triphosphate (ATP) is a central mediator of cancer cell metabolism and signaling, driving processes such as proliferation, invasion, metastasis, and therapeutic resistance. Current ATP imaging modalities-including fluorescence, chemiluminescence/bioluminescence, photoacoustic imaging, and magnetic resonance imaging (MRI)-face inherent trade-offs among sensitivity, spatial resolution, and tissue penetration capability. Here, a dual-mode probe is reported that synergistically couples the anatomical resolution of MRI with the high-sensitive, long-lasting signals of afterglow imaging for visualization of ATP in the tumor microenvironment. The probe is constructed via DNA hybridization between an afterglow unit and a T 1 -weighted MRI contrast agent, with an ATP-specific aptamer mediating probe disassembly upon ATP binding. This design generates simultaneous turn-on afterglow and MRI signals, enabling the imaging of intracellular and extracellular ATP fluctuations. Metabolic modulators-coenzyme Q10 (an ATP activator) and 2-deoxy-D-glucose (2-DG, a glycolysis inhibitor)-are applied to demonstrate dynamic, bidirectional tracking of ATP levels in vivo. Furthermore, by monitoring ATP depletion during synergistic metabolic therapy (cisplatin + 2-DG), a correlation between imaging readouts and therapeutic efficacy is established. The work provides anintegrated MRI/afterglow imaging platform for high-contrast, real-time ATP sensing in cancer, offering a powerful tool for elucidating tumor metabolism and evaluating metabolic interventions.