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

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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
Publication statusPublished - 25 May 2012
Externally publishedYes

Cite this

Verdoes, M., Edgington, L. E., Scheeren, F. A., Leyva, M., Blum, G., Weiskopf, K., Bachmann, M. H., Ellman, J. A., & Bogyo, M. (2012). A nonpeptidic cathepsin s activity-based probe for noninvasive optical imaging of tumor-associated macrophages. Chemistry and Biology, 19(5), 619-628. https://doi.org/10.1016/j.chembiol.2012.03.012