Volume 138, Issue 4, Pages 1266-1275 (April 2010) Epithelial Uptake of [18F]1-(2′-Deoxy-2′-Arabinofuranosyl) Cytosine Indicates Intestinal Inflammation in Mice  Sarah Brewer, Evan Nair–Gill, Bo Wei, Ling Chen, Xiaoxiao Li, Mireille Riedinger, Dean O. Campbell, Stephanie Wiltzius, Nagichettiar Satyamurthy, Michael E. Phelps, Caius Radu, Owen N. Witte, Jonathan Braun  Gastroenterology  Volume 138, Issue 4, Pages 1266-1275 (April 2010) DOI: 10.1053/j.gastro.2010.01.003 Copyright © 2010 AGA Institute Terms and Conditions

Figure 1 Intestinal localization of D-FAC in vivo. (A) Coronal, sagittal, and transverse views of CT and PET overlays and PET alone of wild-type C57Bl/6 mice highlighting the duodenum signal. (B) Gamma counts of different intestinal regions on a per centimeter basis. Each symbol represents a section from an individual mouse. (C) Comparison of %ID/g of ROIs in the intestine (si, jejunum and ileum) with organs known for high D-FAC uptake (spleen and bone marrow). (D) Comparison of duodenum ROIs between β7-/-, germ-free (gf), WT, and colitic mice induced by transfer of Gαi2-/- CD3+ T cells into RAG-/- mice (Gαi2-/-). Gastroenterology 2010 138, 1266-1275DOI: (10.1053/j.gastro.2010.01.003) Copyright © 2010 AGA Institute Terms and Conditions

Figure 2 Cellular source of intestinal signal. (A) %ID/g quantification of small and large intestine ROIs in β7-/- and WT mice. (B) Gamma counts per minute of [18F]-D-FAC uptake in intestinal immune cells, combined IELs and LPLs, and epithelial cells from both the large and small intestines. Four mice were analyzed for each cell population. (C) Gamma counts of immune cells (IELs and LPLs combined for 4 mice) positively selected for the indicated markers. Gastroenterology 2010 138, 1266-1275DOI: (10.1053/j.gastro.2010.01.003) Copyright © 2010 AGA Institute Terms and Conditions

Figure 3 D-FAC intestinal signal in germ-free and colitic mice. (A) Coronal views of PET and CT overlay and PET alone for germ-free (gf), WT, and Gαi2-/- CD3+ transfer mice (Gαi2-/-). Comparison of (B) small and (C) large intestine ROIs, and of peripheral immune organs, the (D) spleen and (E) bone marrow in 3 types of mice. Gastroenterology 2010 138, 1266-1275DOI: (10.1053/j.gastro.2010.01.003) Copyright © 2010 AGA Institute Terms and Conditions

Figure 4 Cellular source of intestinal signal in Gαi2-/- mice. (A–C) Gamma counts of [18F]-D-FAC uptake in isolated intestinal lymphocytes (combined IELs and LPLs) and epithelial cells from large and small intestines of Gαi2-/- mice. Four mice were analyzed for each cell population. (A and B) Counts from all recovered cells in (A) linear and (B) log scale. (C) Counts per cell. (D) PET image of excised intestine. Gastroenterology 2010 138, 1266-1275DOI: (10.1053/j.gastro.2010.01.003) Copyright © 2010 AGA Institute Terms and Conditions

Figure 5 Evaluation of colitis over time with D-FAC and FDG. (A) Coronal views of CT and PET overlay and PET alone at 1 week posttransfer of WT CD3+ or Gαi2-/- CD3+. (B) Coronal views at 3 weeks posttransfer of cells. (C) Graph of weight change as an indicator of disease between mice at 1 and 3 weeks posttransfer. (D) Large intestine ROI compared between time points in mince (1 and 3 weeks posttransfer, as labeled) (Gai2-/- CD3+ transfer in black, WT CD3+ transfer in white). (E) Small intestine ROI compared between time points and transfer mice. (F) Bone marrow ROI compared between time points and transfer mice. Gastroenterology 2010 138, 1266-1275DOI: (10.1053/j.gastro.2010.01.003) Copyright © 2010 AGA Institute Terms and Conditions