A nonpeptidic cathepsin S activity-based probe for noninvasive optical imaging of tumor-associated macrophages.
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.
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Martijn
M
Verdoes
Laura E
LE
Edgington
Ferenc A
FA
Scheeren
Melissa
M
Leyva
Galia
G
Blum
Kipp
K
Weiskopf
Michael H
MH
Bachmann
Jonathan A
JA
Ellman
Matthew
M
Bogyo
D000818:Animals; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D002403:Cathepsins / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D011379:Prognosis
D005456:Fluorescent Dyes; D002403:Cathepsins; C028217:cathepsin S