Journal
BIOCONJUGATE CHEMISTRY
Volume 28, Issue 8, Pages 2069-2076Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.bioconjchem.7b00233
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Funding
- AMED-CREST, JST, PRESTO [JPMJPR14F8]
- MEXT/JSPS KAKENHI grant [JP16H02606, JP26111012, JP15H05951]
- JSPS Core-to-Core Program, Advanced Research Networks
- Hoansha Foundation
- Uehara Memorial Foundation
- Japan Foundation for Applied Enzymology
- Grants-in-Aid for Scientific Research [26111012, 15H05951, 16H02606] Funding Source: KAKEN
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Technology to visualize small prostate cancers is urgently needed because of the difficulty of discriminating prostate cancer from normal tissue with the naked eye, and a fluorescence imaging method would be advantageous. Here, we describe the design and synthesis of a fluorogenic probe (Ac-KQLR-HMRG) that is activated by hepsin and matriptase (proteases over-expressed in prostate cancer). Ac-KQLR-HMRG exhibited significant turn-on fluorogenicity in the presence of hepsin (180-fold) and matriptase (80-fold) and allowed specific fluorescence imaging of various prostate cancer cell line in vitro. In addition, the probe enabled rapid imaging (within 1-10 min) of small prostate cancer nodules in mouse models of disseminated peritoneal tumor and orthotopic tumor.
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