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.