Targeting cathepsin E in pancreatic cancer by a small molecule allows in vivo detection Journal Article
| Authors: | Keliher, E. J.; Reiner, T.; Earley, S.; Klubnick, J.; Tassa, C.; Lee, A. J.; Ramaswamy, S.; Bardeesy, N.; Hanahan, D.; DePinho, R. A.; Castro, C. M.; Weissleder, R. |
| Article Title: | Targeting cathepsin E in pancreatic cancer by a small molecule allows in vivo detection |
| Abstract: | 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. © 2013 Neoplasia Press, Inc. All rights reserved. |
| Keywords: | immunohistochemistry; controlled study; human tissue; unclassified drug; human cell; nonhuman; flow cytometry; mouse; reverse transcription polymerase chain reaction; confocal microscopy; immunofluorescence; simulation; western blotting; pancreas adenocarcinoma; contrast medium; high performance liquid chromatography; ic 50; molecular docking; liquid chromatography; surface plasmon resonance; chemoradiotherapy; electrospray mass spectrometry; ritonavir; cathepsin e; tetra methyl bodipy |
| Journal Title: | NeoPlasia |
| Volume: | 15 |
| Issue: | 7 |
| ISSN: | 1522-8002 |
| Publisher: | Elsevier Science Inc. |
| Date Published: | 2013-07-01 |
| Start Page: | 684 |
| End Page: | 693 |
| Language: | English |
| DOI: | 10.1593/neo.13276 |
| PROVIDER: | scopus |
| PMCID: | PMC3689232 |
| PUBMED: | 23814481 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 August 2013" - "CODEN: NEOPF" - "Source: Scopus" |
