Research ArticleInfection/Inflammation

18F-FAC PET Selectively Images Liver-Infiltrating CD4 and CD8 T Cells in a Mouse Model of Autoimmune Hepatitis

Jessica R. Salas, Bao Ying Chen, Alicia Wong, Donghui Cheng, John S. Van Arnam, Owen N. Witte and Peter M. Clark
Journal of Nuclear Medicine October 2018, 59 (10) 1616-1623; DOI: https://doi.org/10.2967/jnumed.118.210328

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    Hepatic 18F-FDG, 18F-FAC, and 18F-DFA accumulation is affected in mouse model of autoimmune hepatitis. (A) Histochemical and immunohistochemical analyses of liver sections from vehicle- and ConA-treated mice. Scale bars represent 50 μm. (B and C) Transverse PET/CT images (B) and quantification (C) of vehicle- and ConA-treated mice injected with 18F-FDG, 18F-FAC, and 18F-DFA. Livers are outlined. Quantification represents radiotracer accumulation in liver normalized to background organ. **P < 0.01. ***P < 0.001. ****P < 0.0001. H&E = hematoxylin and eosin; ID = injected dose.

  • FIGURE 2.
    FIGURE 2.

    18F-FDG and 18F-FAC measure liver-infiltrating leukocytes, and 18F-DFA measures hepatocyte inflammation. (A) GLUT1, ribokinase, and dCK immunostained vehicle- and ConA-treated mouse liver sections. Scale bars represent 50 μm. (B) Autoradiographic and histologic analyses of liver sections from vehicle- and ConA-treated mice injected with 18F-FDG, 18F-FAC, or 18F-DFA. (C) Ex vivo accumulation of deoxycytidine in sorted leukocytes from livers of ConA-treated mice. ****P < 0.0001. H&E = hematoxylin and eosin; RBKS = ribokinase.

  • FIGURE 3.
    FIGURE 3.

    Hepatic accumulation of 18F-FDG and 18F-DFA but not 18F-FAC is affected in mouse model of viral hepatitis. (A) Histochemical and immunohistochemical analyses of liver sections from pretreatment and adenovirus-treated mice. Scale bars represent 50 μm. (B and C) Transverse PET/CT images (B) and quantification (C) of pretreatment and adenovirus-treated mice injected with 18F-FDG, 18F-DFA, and 18F-FAC. Quantification represents radiotracer accumulation in liver normalized to background organ. **P < 0.01. ****P < 0.0001. H&E = hematoxylin and eosin; ID = injected dose; ns = not significant.

  • FIGURE 4.
    FIGURE 4.

    Changes in hepatic 18F-FAC accumulation can be used to monitor immunosuppressive drug treatments in mouse model of autoimmune hepatitis. (A) Representative hematoxylin- and eosin-stained liver sections of mice treated with vehicle, ConA, or ConA and dexamethasone. Scale bars represent 50 μm. (B) Transverse PET/CT images of hepatic 18F-FAC accumulation in mice treated with vehicle, ConA, or ConA and Dexa. (C) Quantification of hepatic 18F-FAC accumulation in mice treated with vehicle, ConA, or ConA and Dexa. Quantification represents radiotracer accumulation in liver normalized to background organ. ****P < 0.0001. Dexa = dexamethasone; H&E = hematoxylin and eosin; ID = injected dose; ns = not significant.

  • FIGURE 5.
    FIGURE 5.

    Liver-infiltrating leukocytes in patients with autoimmune hepatitis express dCK. Histochemical and immunohistochemical analyses of liver biopsies from patients with autoimmune hepatitis. Scale bars represent 50 μm. H&E = hematoxylin and eosin.

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