Document Detail


Targeting cathepsin E in pancreatic cancer by a small molecule allows in vivo detection.
MedLine Citation:
PMID:  23814481     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neoplasia (New York, N.Y.)     Volume:  15     ISSN:  1476-5586     ISO Abbreviation:  Neoplasia     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-07-01     Completed Date:  2014-01-30     Revised Date:  2014-11-05    
Medline Journal Info:
Nlm Unique ID:  100886622     Medline TA:  Neoplasia     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  684-93     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Biopsy
Boron Compounds / diagnostic use*
Carcinoma, Pancreatic Ductal / diagnosis,  metabolism*,  pathology
Cathepsin E / antagonists & inhibitors,  metabolism*
Cell Line, Tumor
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Fluorescent Dyes / diagnostic use*
HIV Protease Inhibitors / diagnostic use*,  pharmacology
Humans
Inhibitory Concentration 50
Mice
Pancreatic Neoplasms / diagnosis,  metabolism*,  pathology
Ritonavir / analogs & derivatives,  diagnostic use*,  pharmacology
Grant Support
ID/Acronym/Agency:
2P01CA117969/CA/NCI NIH HHS; 2P50CA086355/CA/NCI NIH HHS; P01-AI54904/AI/NIAID NIH HHS; S10 RR026360/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; 0/Boron Compounds; 0/Fluorescent Dyes; 0/HIV Protease Inhibitors; EC 3.4.23.34/Cathepsin E; O3J8G9O825/Ritonavir
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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