Highly Selective Dual-Modal Probe for Photoacoustic and Magnetic Resonance Imaging of the Labile Cu Pool in the Liver.

Copper ions (Cu) play vital roles in human physiology, and their dyshomeostasis is associated with diseases such as hepatocellular carcinoma, Alzheimer's disease, and Wilson's disease. Cu imaging technologies facilitate the investigation of Cu dynamics in biological systems. However, developing highly selective and sensitive Cu probes that can overcome interference from physiologically abundant Zn remains a key challenge. In this study, we design and synthesize a Cu-activated dual-modal probe () for photoacoustic (PA) and magnetic resonance (MR) imaging, which exhibits remarkable specificity for Cu. Impressively, demonstrates exceptional selectivity for Cu even in the presence of a 1000-fold excess of Zn. binds Cu in a 1:1 stoichiometry, forming a stable ternary complex in the presence of human serum albumin (HSA), which enhances PA signals by 5.9-fold and increases longitudinal relaxivity () by 114.9%. Furthermore, experiments demonstrate that enables precise monitoring of labile Cu fluctuations in the liver of mice, achieving a remarkable 59% increase in PA signal intensity and a 30% enhancement in MR signal contrast. The systematic investigation demonstrates that can serve as a powerful molecular probe for investigating copper metabolism in living systems. Our breakthrough addresses the long-standing challenge of Cu/Zn discrimination and provides a design principle for next-generation metal ion probes, with significant potential for diagnosing Cu imbalance-related disorders, monitoring therapeutic responses, and advancing biomedical research.