Lanthanide Complexes-Based Probe for Dual-Modal Time-Gated Luminescence and Magnetic Resonance Imaging of Physiological pH Fluctuations

Monitoring pH fluctuations with high sensitivity and spatiotemporal resolution is essential for understanding their roles in physiology and pathology; however, existing approaches are often limited by invasiveness, low sensitivity, or inadequate tissue penetration. Here we report the design and synthesis of pH-Eu/Gd, a small-molecule lanthanide complex that integrates time-gated luminescence (TGL) and magnetic resonance (MR) readouts for dual-modal pH sensing. Constructed by chelating quinolinesulfonamide-DO3A ligands with Eu3+ and Gd3+ ions, pH-Eu/Gd exhibits complementary pH-dependent luminescence intensity/lifetime and proton relaxivity changes, arising from modulation of the probe’s hydration state. The probe demonstrates excellent photostability and a rapid, reversible, and selective response to pH variations across the biologically relevant range. In live cells, pH-Eu/Gd effectively tracked intracellular pH fluctuations; while in vivo, it visualized intratumoral acidosis and enabled noninvasive monitoring of buffering therapy responses, with TGL imaging providing histological-scale validation of MR findings. Furthermore, oral administration of pH-Eu/Gd allowed dynamic tracking of gastric juice pH and antacid treatment efficacy. Together, these results establish pH-Eu/Gd as a versatile dual-modal probe for noninvasive pH sensing, expanding the scope of lanthanide complex-based molecular sensors and offering a new strategy for preclinical applications in oncology, gastroenterology, and beyond.