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Title: Non-Invasive Imaging of Cysteine Cathepsin Activity in Solid Tumors Using a Cu-64-Labeled Activity-Based Probe
Authors: Ren, Gang ×
Blum, Galia
Verdoes, Martijn
Liu, Hongguang
Syed, Salahuddin
Edgington, Laura E
Gheysens, Olivier
Miao, Zheng
Jiang, Han
Gambhir, Sanjiv Sam
Bogyo, Matthew
Cheng, Zhen #
Issue Date: Nov-2011
Publisher: Public Library of Sciene
Series Title: PLoS One vol:6 issue:11 pages:-
Article number: e28029
Abstract: The papain family of cysteine cathepsins are actively involved in multiple stages of tumorigenesis. Because elevated cathepsin activity can be found in many types of human cancers, they are promising biomarkers that can be used to target radiological contrast agents for tumor detection. However, currently there are no radiological imaging agents available for these important molecular targets. We report here the development of positron emission tomography (PET) radionuclide-labeled probes that target the cysteine cathepsins by formation of an enzyme activity-dependent bond with the active site cysteine. These probes contain an acyloxymethyl ketone (AOMK) functional group that irreversibly labels the active site cysteine of papain family proteases attached to a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) tag for labeling with Cu-64 for PET imaging studies. We performed biodistribution and microPET imaging studies in nude mice bearing subcutaneous tumors expressing various levels of cysteine cathepsin activity and found that the extent of probe uptake by tumors correlated with overall protease activity as measured by biochemical methods. Furthermore, probe signals could be reduced by pre-treatment with a general cathepsin inhibitor. We also found that inclusion of a Cy5 tag on the probe increased tumor uptake relative to probes lacking this fluorogenic dye. Overall, these results demonstrate that small molecule activity-based probes carrying radio-tracers can be used to image protease activity in living subjects.
URI: 
ISSN: 1932-6203
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

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