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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

96 Scopus citations


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 languageAmerican English
Pages (from-to)619-628
Number of pages10
JournalChemistry and Biology
Issue number5
StatePublished - 25 May 2012

Bibliographical note

Funding Information:
We thank J. Lee for help with synthesis, A. W. Puri for assistance with macrophage isolation, and M. A. Child and E. Due for critical discussions. We also thank T. Doyle at the Stanford Small Animal Facility at Stanford for assistance with optical imaging studies and S. R. Lynch at the Stanford University Department of Chemistry NMR facility for assistance. This work was supported by the National Institutes of Health (grants R01 EB005011 and R01 AI078947 to M.B.). M.V. is supported by a Rubicon fellowship from the Netherlands Organization for Scientific Research (NWO).


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