Fluorine-19 Magnetic Resonance Imaging and Positron Emission Tomography of Tumor-Associated Macrophages and Tumor Metabolism

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 (18)F-2-fluoro-2-deoxy-D-glucose ((18)F-FDG) as a radioactive tracer and fluorine-19- ((19)F-) 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,( 18)F-FDG-PET images were acquired immediately after (19)F-MRI. Coregistered (18)F-FDG-PET and (19)F-MR images enabled comparison of spatial patterns of glucose uptake and TAM distribution in tumors. (19)F-MR signal intensities from tumors exhibited a strong inverse correlation with (18)F-FDG uptake while having a significant positive correlation with tumor growth from days 2 to 7. These results show that combination of (19)F-MRI and (18)F-FDG-PET can improve our understanding of the relationship between TAM and tumor microenvironment.