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 3

Cell-intrinsic [3H]-2DG accumulation is highest in innate immune cells, while [3H]-FAC accumulates predominantly in adaptive immune cells.

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Cell-intrinsic [3H]-2DG accumulation is highest in innate immune cells, ...
(A) Single-cell suspensions of spleen, DLN, and tumor from MSV/MuLV-infected mice were analyzed for CD4, CD8, B220, and CD11b by flow cytometry. Populations that were collected for probe accumulation analysis are boxed in red. Values in the quadrants represent the percentage of major immune lineages isolated from each tissue. (B) The total number of each cell type recovered from the spleen, DLN, and tumor are shown (n = 6 mice). (C and D) Cells (105) from the sorted populations were pulse labeled with [3H]-2DG (C) or [3H]-FAC (D) and compared with naive lymphocytes (***P < 0.0001, *P < 0.05, n = 3 experiments). Sorted cells were fixed and stained with propidium iodide. The percentage in S-G2-M was plotted against the accumulation of [3H]-2DG and [3H]-FAC. Data from 3 experiments are shown. Open, filled, and half-filled symbols represent 3 experiments. Shapes were assigned according to cell type: squares, B cells; triangles, CD4+ T cells; circles, CD8+ T cells; diamonds, CD11bhi myeloid cells. Colors were assigned based on the tissues from which a cell population was isolated: blue, spleen; green, DLN; red, tumor; gray, naive lymph nodes. A positive correlation between [3H]-FAC accumulation and percent in S-G2-M was observed (r2 = 0.68, P < 0.0001).