A nonpeptidic cathepsin s activity-based probe for noninvasive optical imaging of tumor-associated macrophages

Martijn Verdoes, Laura E. Edgington, Ferenc A. Scheeren, Melissa Leyva, Galia Blum, Kipp Weiskopf, Michael H. Bachmann, Jonathan A. Ellman, Matthew Bogyo

Research output: Contribution to journalArticlepeer-review

Abstract

Macrophage infiltration into tumors has been correlated with poor clinical outcome in multiple cancer types. Therefore, tools to image tumor-associated macrophages could be valuable for diagnosis and prognosis of cancer. Herein, we describe the synthesis and characterization of a cathepsin S-directed, quenched activity-based probe (qABP), BMV083. This probe makes use of an optimized nonpeptidic scaffold leading to enhanced in vivo properties relative to previously reported peptide-based probes. In a syngeneic breast cancer model, BMV083 provides high tumor-specific fluorescence that can be visualized using noninvasive optical imaging methods. Furthermore, analysis of probe-labeled cells demonstrates that the probe primarily targets macrophages with an M2 phenotype. Thus, BMV083 is a potential valuable in vivo reporter for tumor-associated macrophages that could greatly facilitate the future studies of macrophage function in the process of tumorigenesis.

Original languageEnglish
Pages (from-to)619-628
Number of pages10
JournalChemistry and Biology
Volume19
Issue number5
DOIs
StatePublished - 25 May 2012

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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