Visualization of macrophage recruitment in head and neck carcinoma model using fluorine-19 magnetic resonance imaging

Purpose: To evaluate the role of infiltrating macrophages in murine models of single and double mutation head and neck tumors using a novel fluorine-19 (¹⁹ F) MRI technology.

Methods: Tumor cell lines single-hit/SCC4 or double-hit/Cal27, with mutations of TP53 and TP53 & FHIT, respectively, were injected bilaterally into the flanks of (n = 10) female mice. With tumors established, perfluorocarbon nanoemulsion was injected intravenously, which labels in situ predominantly monocytes and macrophages. Longitudinal spin density-weighted ¹⁹ F MRI data enabled quantification of the macrophage burden in tumor and surrounding tissue.

Results: The average number of ¹⁹ F atoms within the tumors was twice as high in the Cal27 group compared with SCC4 (3.9 × 10¹⁹ and 2.0 × 10¹⁹¹⁹ F/tumor, respectively; P = 0.0034) two days after contrast injection, signifying increased tumor-associated macrophages in double-hit tumors. The difference was still significant 10 days after injection. Histology stains correlated with in vivo results, exhibiting numerous perfluorocarbon-labeled macrophages in double-hit tumors and to a lesser extent in single-hit tumors.

Conclusions: This study helps to establish ¹⁹ F MRI as a method for quantifying immune cells in the tumor microenvironment, allowing distinction between double and single-hit head and neck tumors. This technique would be extremely valuable in the clinic for pretreatment planning, prognostics, and post-treatment surveillance. Magn Reson Med 79:1972-1980, 2018. © 2017 International Society for Magnetic Resonance in Medicine.