In-vivo imaging of tumor associated urokinase-type plasminogen activator activity.
The ability to image tumor associated protease in vivo has biological and clinical implications. In the present study, we describe the development and validation of a urokinase-type plasminogen activator (uPA) sensitive fluorescence imaging probe. The activation of our probe is highly specific to uPA in both enzymatic and cellular-based assays. In two distinct in-vivo tumor models (human colon adenocarcinoma HT-29 and human fibrosarcoma HT-1080), the observed fluorescence changes correlate well with tumor associated uPA activity. The signal intensities of the tumors are about three-fold higher in animals with probe injections. Our results suggest a direct detection method for uPA activity in vivo and the approach can be used for monitoring tumor growth and development.
Hsiao
Jong-Kai
JK
Massachusetts General Hospital, Harvard Medical School, Center for Molecular Imaging Research, Charlestown, 02129, USA.
Law
Benedict
B
Weissleder
Ralph
R
Tung
Ching-Hsuan
CH
D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D005354:Fibrosarcoma / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D008856:Microscopy, Fluorescence / Q000379:methods*; D009363:Neoplasm Proteins / Q000032:analysis*; D013055:Spectrophotometry, Infrared / Q000379:methods; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis*
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D014568:Urokinase-Type Plasminogen Activator