Journal
CANCER RESEARCH
Volume 73, Issue 2, Pages 855-864Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-12-2969
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Funding
- patent filing by University of California San Diego
- Howard Hughes Medical Institute
- ICMIC [NCI-P50-CA128346]
- Burrough-Wellcome Fund (CAMS) [5R25CA153915]
- NIH [5K08EB008122, R01 CA158448]
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Management of metastatic disease is integral to cancer treatment. Evaluation of metastases often requires surgical removal of all anatomically susceptible lymph nodes for ex vivo pathologic examination. We report a family of novel ratiometric activatable cell-penetrating peptides, which contain Cy5 as far red fluorescent donor and Cy7 as near-infrared fluorescent acceptor. Cy5 is quenched in favor of Cy7 reemission until the intervening linker is cut by tumor-associated matrix metalloproteinases-2 and 9 (MMP2,9) or elastases. Such cleavage increases the Cy5: Cy7 emission ratio 40-fold and triggers tissue retention of the Cy5-containing fragment. This ratiometric increase provides an accelerated and quantifiable metric to identify primary tumors and metastases to liver and lymph nodes with increased sensitivity and specificity. This technique represents a significant advance over existing nonratiometric protease sensors and sentinel lymph node detection methods, which give no information about cancer invasion. Cancer Res; 73(2); 855-64. (C) 2012 AACR.
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