Dynamic Photoacoustic Imaging of Mobile Cu(II) in Vivo via Catalytic Radical Cation Formation

Abstract Copper dyshomeostasis is associated with various diseases, making in vivo spatiotemporal imaging of mobile Cu(II) dynamics crucial for understanding pathophysiological mechanisms. However, imaging mobile Cu(II) dynamics remains a long‐standing challenge due to the limitations of conventional probes in distinguishing between mobile and bound Cu(II). Herein, we developed a design strategy based on catalytic arylamine radical cation formation, enabling the creation of photoacoustic probes with superior sensitivity and micron‐resolution imaging capabilities in the short‐wave infrared region, specifically in response to mobile Cu(II). In vivo imaging of the brains of Parkinson's disease model mice revealed significant alternations in mobile Cu(II) levels within the cerebral cortex and cerebellar lobules during early disease stages, suggesting that these regions are particularly vulnerable to Cu(II) accumulation in early Parkinson's disease. These findings underscore the significant potential of these probes for investigating mobile Cu(II) dynamics and their role in physiological and pathological processes.