Development of a Dual Factor Activatable Covalent Targeted Photoacoustic Imaging Probe for Tumor Imaging

Photoacoustic imaging (PAI) is an emerging modality in biomedical imaging with superior imaging depth and specificity. However, PAI still has significant limitations, such as the background noise from endogenous chromophores. To overcome these limitations, we developed a covalent activity‐based PAI probe, NOx‐JS013, targeting NCEH1. NCEH1, a highly expressed and activated serine hydrolase in aggressive cancers, has the potential to be employed for the diagnosis of cancers. We show that NOx‐JS013 labels active NCEH1 in live cells with high selectivity relative to other serine hydrolases. NOx‐JS013 also presents its efficacy as a hypoxia‐responsive imaging probe in live cells. Finally, NOx‐JS013 successfully visualizes aggressive prostate cancer tumors in mouse models of PC3, while negligibly detected in tumors of non‐aggressive LNCaP mouse models. These findings show that NOx‐JS013 has the potential to be used to develop precision PAI reagents for detecting metastatic progression in various cancers.