PET probes for distinct metabolic pathways have different cell specificities during immune responses in mice
Evan Nair-Gill, … , Caius G. Radu, Owen N. Witte
Evan Nair-Gill, … , Caius G. Radu, Owen N. Witte
Published May 17, 2010
Citation Information: J Clin Invest. 2010;120(6):2005-2015. https://doi.org/10.1172/JCI41250.
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PET probes for distinct metabolic pathways have different cell specificities during immune responses in mice

Abstract

Clinical tools that measure changes in immune cell metabolism would improve the diagnosis and treatment of immune dysfunction. PET, utilizing probes for specific metabolic processes, detects regions of immune activation in vivo. In this study we investigated the immune cell specificity of PET probes for two different metabolic pathways: [18F]–2-fluorodeoxyglucose ([18F]-FDG) for glycolysis and [18F]–2-fluoro-d-(arabinofuranosyl)cytosine ([18F]-FAC) for deoxycytidine salvage. We isolated innate and adaptive immune cells from tissues of mice challenged with a retrovirus-induced sarcoma and measured their ability to accumulate FDG and FAC. We determined that the two probes had distinct patterns of accumulation: FDG accumulated to the highest levels in innate immune cells, while FAC accumulated predominantly in CD8+ T cells in a manner that correlated with cellular proliferation. This study demonstrates that innate and adaptive cell types differ in glycolytic and deoxycytidine salvage demands during an immune response and that these differential metabolic requirements can be detected with specific PET probes. Our findings have implications for the interpretation of clinical PET scans that use [18F]-FDG or [18F]-FAC to assess immune function in vivo and suggest potential applications of metabolic PET to monitor the effects of targeted immune modulation.

Authors

Evan Nair-Gill, Stephanie M. Wiltzius, Xiao X. Wei, Donghui Cheng, Mireille Riedinger, Caius G. Radu, Owen N. Witte

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Figure 2

Inoculation with MSV/MuLV leads to increased density of diverse immune cell types in lymphoid organs and transformed muscle tissue.

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Inoculation with MSV/MuLV leads to increased density of diverse immune c...
(A) Tumor, DLN, and spleens were harvested from MSV/MuLV-infected mice 14 days after inoculation, at the peak of the antitumor response, sectioned, and stained with antibodies for CD4, CD8, B220, and CD11b (original magnification: ×20; insets, ×40). Corresponding tissue from uninfected mice were stained for comparison. (B) Quantification of the density of positively stained cells in tissues from naive and MSV/MuLV-infected mice (3 sections for each stain). (C) Whole-body coronal sections for autoradiographic validation of [18F]-FDG and [18F]-FAC accumulation in tissues during MSV/MuLV infection (asterisk indicates saturated region on detector). Mu/T, muscle/tumor; Li, liver.