Cathepsin K‐Activated Probe for Fluoro‐Photoacoustic Imaging of Early Osteolytic Metastasis

Precise detection of early osteolytic metastases is crucial for their treatment but remains challenging in the clinic because of the limited sensitivity and specificity of traditional imaging techniques. Although fluorescence imaging offers attractive features for the diagnosis of osteolytic metastases, it is hampered by limited penetration depth. To address this issue, a fluoro‐photoacoustic dual‐modality imaging probe comprising a near‐infrared dye caged by a cathepsin K (CTSK)‐cleavable peptide sequence on one side and functionalized with osteophilic alendronate through a polyethylene glycol linker on the other side is reported. Through systematic in vitro and in vivo experiments, it is demonstrated that in response to CTSK, the probe generated both near‐infrared fluorescent and photoacoustic signals from bone metastatic regions, thus offering a potential strategy for detecting deep‐seated early osteolytic metastases.