Quantifying tumor associated macrophages in breast cancer: a comparison of iron and fluorine-based MRI cell tracking

Tumor associated macrophages (TAMs) are associated with tumor growth and metastasis. MRI can detect TAMs labeled with iron oxide (USPIO) or perfluorocarbon (PFC) agents. This study compared these two cell tracking approaches for imaging TAMs in vivo. 4T1 tumors were imaged with MRI at 4 days or 3 weeks post cell implantation after intravenous (i.v.) administration of either USPIO or PFC. Signal loss was detected within tumors at both time points post USPIO. Images acquired at 4 days demonstrated signal loss encompassing the entire tumor and around the periphery at 3 weeks. Number of black voxels suggested higher numbers of TAMs in the tumor at the later time point. After PFC administration, Fluorine-19 ((19)F) signal was detected in a similar spatial distribution as signal loss post USPIO. (19)F signal quantification revealed that the number of (19)F spins was not significantly different at the two time points, suggesting a similar number of TAMs were present in tumors but accumulated in different regions. (19)F signal was higher centrally in tumors at 4 days and heterogenous around the periphery at 3 weeks. This study revealed that (19)F-based cell tracking methods better represent TAM density and provides additional information not achievable with iron-based methods.