Aman Khurana1, Fanny Chapelin2, Hongyan Xu1, Joseph R Acevedo3, Alfred Molinolo4, Quyen Nguyen5, Eric T Ahrens1. 1. Department of Radiology, University of California San Diego, La Jolla, California, USA. 2. Department of Bioengineering, University of California San Diego, La Jolla, California, USA. 3. School of Medicine, University of California San Diego, La Jolla, California, USA. 4. Department of Pathology, University of California San Diego, La Jolla, California, USA. 5. Department of Head and Neck Surgery, University of California San Diego, La Jolla, California, USA.
Abstract
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.
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.
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