Abstract
The presence of tumor-associated macrophages (TAMs) is significantly associated with poor prognosis of tumors. Currently, magnetic resonance imaging- (MRI-) based TAM imaging methods that use nanoparticles such as superparamagnetic iron oxide and perfluorocarbon nanoemulsions are available for quantitative monitoring of TAM burden in tumors. However, whether MRI-based measurements of TAMs can be used as prognostic markers has not been evaluated yet. In this study, we used positron emission tomography (PET) with 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) as a radioactive tracer and fluorine-19- (19F-) MRI for imaging mouse breast cancer models to determine any association between TAM infiltration and tumor metabolism. Perfluorocarbon nanoemulsions were intravenously administered to track and quantify TAM infiltration using a 7T MR scanner. To analyze glucose uptake in tumors, 18F-FDG-PET images were acquired immediately after 19F-MRI. Coregistered 18F-FDG-PET and 19F-MR images enabled comparison of spatial patterns of glucose uptake and TAM distribution in tumors. 19F-MR signal intensities from tumors exhibited a strong inverse correlation with 18F-FDG uptake while having a significant positive correlation with tumor growth from days 2 to 7. These results show that combination of 19F-MRI and 18F-FDG-PET can improve our understanding of the relationship between TAM and tumor microenvironment.
Highlights
Many types of tumors with poor prognosis are characterized by dense infiltration of tumor-associated macrophages (TAMs) [1,2,3]
In positron emission tomography (PET) images, standardized uptake values (SUVs) hypointensities were observed at the centers of tumors, which corresponded to hyperintense signals observed in T2-weighted MR images (Figures 2(b) and 2(c))
Preliminary results from combining 19F-magnetic resonance imaging (MRI) and 18F-FDG-PET suggest that 19F-MRI tracking of TAMs might aid the characterization of tumors and prediction of tumor development
Summary
Many types of tumors with poor prognosis are characterized by dense infiltration of tumor-associated macrophages (TAMs) [1,2,3]. Several imaging methods have been developed for noninvasive analysis of distribution and quantification of TAMs in tumors. One of these methods is the nanoparticle-based magnetic resonance imaging (MRI) cell-tracking method, which exploits the high phagocytic activity of macrophages to passively label them with nanoparticles through intravenous administration. Superparamagnetic iron oxide (SPIO) nanoparticles and perfluorocarbon (PFC) nanoemulsions are widely used as TAM-labeling contrast agents. With SPIO nanoparticles, TAMs are visualized as hypointense spots on T2-weighted MR images. These nanoparticles have a high potential for clinical translation owing to their approval by the Food and Drug Administration (e.g., Feraheme) [13, 14]. Because of the lack of 19F atoms in biological tissues, 19F-MRI confirms the presence of TAMs once 19F signals
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