Targeting cathepsin E in pancreatic cancer by a small molecule allows in vivo detection Academic Article Article uri icon

Overview

MeSH Major

  • Antineoplastic Agents
  • Attitude to Health
  • Drug-Related Side Effects and Adverse Reactions
  • Neoplasm Recurrence, Local
  • Ovarian Neoplasms
  • Patient Care Planning
  • Quality of Life
  • Survivors

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.

publication date

  • July 2013

Research

keywords

  • Academic Article

Identity

Digital Object Identifier (DOI)

  • 10.1593/neo.13276

PubMed ID

  • 23814481

Additional Document Info

start page

  • 684

end page

  • 93

volume

  • 15

number

  • 7