Journal
CHEMISTRY & BIOLOGY
Volume 11, Issue 1, Pages 99-106Publisher
CELL PRESS
DOI: 10.1016/j.chembiol.2003.12.017
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Funding
- NCI NIH HHS [R01 CA99385, N01-CO17016, P50-CA86355] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [R01CA099385, P50CA086355] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DENTAL &CRANIOFACIAL RESEARCH [Z01DE000699] Funding Source: NIH RePORTER
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The urokinase-type plasminogen activator (uPA) plays a critical role in malignancies, and its overexpression has been linked to poor clinical prognosis in breast cancer. The ability to noninvasively and serially map uPA expression as a biomarker would thus have significant potential in improving novel cancer therapies. Here, we describe the development of a selective uPA activatable near-infrared (NIR) fluorescent imaging probe. The probe consists of multiple peptide motifs, GGSGRSANAKC-NH2, terminally capped with different NIR fluorochromes (Cy5.5 or Cy7) and a pegylated poly-L-lysine graft copolymer. Upon addition of recombinant human uPA to the probe, significant fluorescence amplification was observed, up to 680% with the optimized preparation. No activation with negative control compounds and uPA inhibitors could be measured. These data indicate that the optimized preparation should be useful for imaging uPA in cancer.
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