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

Abstract 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.