Targeting Cathepsin E in Pancreatic Cancer by a Small Molecule Allows In Vivo Detection
| Autor: | Edmund J. Keliher, Thomas Reiner, Sarah Earley, Jenna Klubnick, Carlos Tassa, Andrew J. Lee, Sridhar Ramaswamy, Nabeel Bardeesy, Douglas Hanahan, Ronald A. DePinho, Cesar M. Castro, Ralph Weissleder |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: | |
| Zdroj: | Neoplasia: An International Journal for Oncology Research, Vol 15, Iss 7, Pp 684-693 (2013) |
| Druh dokumentu: | article |
| ISSN: | 1476-5586 1522-8002 |
| DOI: | 10.1593/neo.13276 |
| Popis: | When resectable, invasive pancreatic ductal adenocarcinoma (PDAC) is most commonly treated with surgery and radiochemotherapy. Given the intricate local anatomy and locoregional mode of dissemination, achieving clean surgical margins can be a significant challenge. On the basis of observations that cathepsin E (CTSE) is overexpressed in PDAC and that an United States Food and Drug Administration (FDA)-approved protease inhibitor has high affinity for CTSE, we have developed a CTSE optical imaging agent [ritonavir tetramethyl-BODIPY (RIT-TMB)] for potential intraoperative use.We show nanomolar affinity [half maximal inhibitory concentration (IC50) of 39.9 ± 1.2 nM] against CTSE of the RIT-TMB in biochemical assays and intracellular accumulation and target-to-background ratios that allow specific delineation of individual cancer cells. This approach should be useful for more refined surgical staging, planning, and resection with curative intent. |
| Databáze: | Directory of Open Access Journals |
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