Cathepsin B-Activated PET Tracer for In Vivo Tumor 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 SF scaffold has been reported to detect the activity of a variety of tumor-associated enzymes. In this work, a small-molecule PET tracer ( [ 68 Ga]NOTA-SF-CV ) was developed by combining an SF scaffold with a cathepsin B-specific recognition substrate Cit-Val. Upon activation by cathepsin B, [ 68 Ga]NOTA-SF-CV could 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, [ 68 Ga]NOTA-SF-CV had great targeting specificity to cathepsin B. In vivo microPET imaging results showed that [ 68 Ga]NOTA-SF-CV was able to effectively visualize the expression level of cathepsin B in various tumors. Hence, [ 68 Ga]NOTA-SF-CV may be served as a potential tracer for diagnosing cathepsin B-related diseases.