Behavior of endogenous tumor-associated macrophages assessed in vivo using a functionalized nanoparticle

Antoine Leimgruber, Cedric Berger, Virna Cortez-Retamozo, Martin Etzrodt, Andita Newton, Peter Waterman, Jose-Luiz Figueiredo, Rainer Kohler, Natalie Elpek, Thorsten R Mempel, Filip K Swirski, Matthias Nahrendorf, Ralph Weissleder and Mikael J Pittet

Year 2009, Volume 11, Issue 5

Abstract

Tumor-associated macrophages (TAM) invade the tumor stroma in many cancers, yet their role is incompletely understood. To visualize and better understand these critical cells in tumor progression, we screened a portfolio of rationally selected, injectable agents to image endogenous TAM ubiquitously in three different cancer models (colon carcinoma, lung adenocarcinoma and soft tissue sarcoma). AMTA680, a functionally derivatized magnetofluorescent nanoparticle, labeled a subset of myeloid cells with a ‘M2’ macrophage phenotype, whereas other neighboring cells, including tumor cells and a variety of other leukocytes, remained unlabeled. We further show that AMTA680–labeled endogenous TAM are not altered and can be tracked noninvasively at different resolutions and using various imaging modalities, e.g., fluorescence molecular tomography, magnetic resonance imaging, and multiphoton and confocal intravital microscopy. Quantitative assessment of TAM distribution and activity in vivo identified that these cells cluster in delimited foci within tumors, show relatively low motility, and extend cytoplasmic protrusions for prolonged physical interactions with neighboring tumor cells. Noninvasive imaging can also be used to monitor TAM–depleting regimen quantitatively. Thus, AMTA680 or related cell-targeting agents represent appropriate injectable vehicles for in vivo analysis of the tumor microenvironment.

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