Cathepsin B Turning Bioluminescence "On" for Tumor Imaging

Anal Chem. 2019 Dec 3;91(23):14834-14837. doi: 10.1021/acs.analchem.9b04254. Epub 2019 Nov 19.

Abstract

Cathepsin B (CTSB) is a lysosomal protease, and several human cancers are reported highly expressing CTSB. Many optical methods have been developed for CTSB detection but not a bioluminescence (BL) probe. Herein, a CTSB-specific bioluminescence probe Val-Cit-AL was rationally designed for selectively sensing CTSB activity in vitro with a 67-fold "Turn-On" of BL intensity and an excellent limit of detection. Inhibitory experiments indicated that Val-Cit-AL is capable of sensing CTSB activity in living cells and tumors. We anticipate that Val-Cit-AL might be applied to diagnose CTSB-related diseases in rodent models or evaluate CTSB roles in more biological processes in the near future.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / antagonists & inhibitors
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / diagnostic imaging*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cathepsin B / antagonists & inhibitors
  • Cathepsin B / genetics*
  • Cathepsin B / metabolism
  • Cell Line, Tumor
  • Diagnostic Imaging / methods*
  • Dipeptides / pharmacology
  • Female
  • Gene Expression
  • Heterografts
  • Humans
  • Luminescent Measurements
  • Lysosomes / drug effects
  • Lysosomes / enzymology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Molecular Probes / chemical synthesis
  • Molecular Probes / pharmacokinetics*

Substances

  • Biomarkers, Tumor
  • CA 074 methyl ester
  • Dipeptides
  • Molecular Probes
  • CTSB protein, human
  • Cathepsin B