Cathepsin B-Activated PET Tracer for In VivoTumor Imaging

Cathepsin B, a lysosomal protease, is considered as a crucial biomarker for tumor diagnosis and treatment as it is overexpressed in numerous cancers. A stimulus-responsive SFscaffold has been reported to detect the activity of a variety of tumor-associated enzymes. In this work, a small-molecule PET tracer ([68Ga]NOTA-SF-CV) was developed by combining an SFscaffold with a cathepsin B-specific recognition substrate Cit-Val. Upon activation by cathepsin B, [68Ga]NOTA-SF-CVcould form the cyclization product in a reduction environment, resulting in reduced hydrophilicity. This unique property could effectively prevent exocytosis of the tracer in cathepsin B-overexpressing tumor cells, leading to prolonged retention and amplified PET imaging signal. Moreover, [68Ga]NOTA-SF-CVhad great targeting specificity to cathepsin B. In vivomicroPET imaging results showed that [68Ga]NOTA-SF-CVwas able to effectively visualize the expression level of cathepsin B in various tumors. Hence, [68Ga]NOTA-SF-CVmay be served as a potential tracer for diagnosing cathepsin B-related diseases.