Elsevier

Neoplasia

Volume 11, Issue 5, May 2009, Pages 459-468, IN3-IN4
Neoplasia

Behavior of Endogenous Tumor-Associated Macrophages Assessed In Vivo Using a Functionalized Nanoparticle1,2

https://doi.org/10.1593/neo.09356Get rights and content
Under a Creative Commons license
open access

Abstract

Tumor-associated macrophages (TAMs) 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 TAMs ubiquitously in three different cancer models (colon carcinoma, lung adenocarcinoma, and soft tissue sarcoma). AMTA680, a functionally derivatized magneto-fluorescent nanoparticle, labeled a subset of myeloid cells with an “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 TAMs 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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1

This work was funded in part by the National Institutes of Health (NIH) U54-CA126515 (to R.W.), NIH 5P50 CA86355 (to R.W. and M.J.P.), NIH U24-CA092782 (to R.W.), NIH U54-CA119349 (to R.W.), and Swiss NSF PBLAB-11555 (to A.L.).

2

This article refers to supplementary materials, which are designated by Figures W1 to W4 and Videos W1 to W3 and are available online at www.neoplasia.com.

3

A.L. and C.B. contributed equally to this work.