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

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background & Aims: Uptake of [18F]1-(2′-deoxy-2′-arabinofuranosyl)cytosine (D-FAC) is a trait of activated lymphocytes; its biodistribution predominates in the spleen, thymus, and bone marrow. In addition, D-FAC is taken up at high levels by the intestine. We analyzed the regional specificity of uptake and cell types that mediate it. Methods: In mice, 3-dimensional isocontour regions of interest were drawn based on computed tomographic images to quantify intestinal signals from micro-positron emission tomography scans. To ascertain the cell type responsible, intestinal epithelium and immune cells were isolated and D-FAC uptake was analyzed in vitro. Mice deficient in mucosal homing (β7 integrin-/-), enteric microbiota (germ-free), or active for immune colitis (Gαi2-/- CD3+ transferred into Rag-/- recipients) were studied. Results: Strong uptake of D-FAC was detected throughout the intestine, with greatest signal per region of interest in the duodenum. Fractionation of intestinal cell types after in vivo uptake revealed that the signal was almost entirely from epithelial cells. Among resident immune cell types, CD4+ T cells showed the greatest per-cell and total uptake. D-FAC uptake increased in both intestinal and systemic lymphoid sites during colitis. Compared with fluorodeoxyglucose, increased uptake of D-FAC in the small and large intestine occurred at an earlier stage of disease development. Conclusions: Uptake of D-FAC is a prominent trait of normal mouse intestinal epithelial cells, which is useful for their noninvasive visualization by positron emission tomography. Increased uptake of D-FAC reflects the activity of the epithelium and lymphocytes, providing a unique early marker of intestinal inflammation.

Original languageEnglish (US)
Pages (from-to)1266-1275
Number of pages10
JournalGastroenterology
Volume138
Issue number4
DOIs
StatePublished - Apr 2010
Externally publishedYes

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Cytosine
Inflammation
Colitis
Positron-Emission Tomography
Intestines
Epithelial Cells
Lymphocytes
Cell Fractionation
Microbiota
Large Intestine
Intestinal Mucosa
(18F)1-(2'-deoxy-2'-arabinofuranosyl)cytosine
Duodenum
Integrins
Thymus Gland
Small Intestine
Spleen
Epithelium
Bone Marrow
T-Lymphocytes

Keywords

  • Cytosine nucleoside
  • Fluorodeoxyglucose
  • Inflammatory bowel disease
  • Positron emission tomography

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Epithelial Uptake of [18F]1-(2′-Deoxy-2′-Arabinofuranosyl) Cytosine Indicates Intestinal Inflammation in Mice. / Brewer, Sarah; Nair-Gill, Evan; Wei, Bo; Chen, Ling; Li, Xiaoxiao; Riedinger, Mireille; Campbell, Dean O.; Wiltzius, Stephanie; Satyamurthy, Nagichettiar; Phelps, Michael E.; Radu, Caius; Witte, Owen N.; Braun, Jonathan.

In: Gastroenterology, Vol. 138, No. 4, 04.2010, p. 1266-1275.

Research output: Contribution to journalArticle

Brewer, S, Nair-Gill, E, Wei, B, Chen, L, Li, X, Riedinger, M, Campbell, DO, Wiltzius, S, Satyamurthy, N, Phelps, ME, Radu, C, Witte, ON & Braun, J 2010, 'Epithelial Uptake of [18F]1-(2′-Deoxy-2′-Arabinofuranosyl) Cytosine Indicates Intestinal Inflammation in Mice', Gastroenterology, vol. 138, no. 4, pp. 1266-1275. https://doi.org/10.1053/j.gastro.2010.01.003
Brewer, Sarah ; Nair-Gill, Evan ; Wei, Bo ; Chen, Ling ; Li, Xiaoxiao ; Riedinger, Mireille ; Campbell, Dean O. ; Wiltzius, Stephanie ; Satyamurthy, Nagichettiar ; Phelps, Michael E. ; Radu, Caius ; Witte, Owen N. ; Braun, Jonathan. / Epithelial Uptake of [18F]1-(2′-Deoxy-2′-Arabinofuranosyl) Cytosine Indicates Intestinal Inflammation in Mice. In: Gastroenterology. 2010 ; Vol. 138, No. 4. pp. 1266-1275.
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abstract = "Background & Aims: Uptake of [18F]1-(2′-deoxy-2′-arabinofuranosyl)cytosine (D-FAC) is a trait of activated lymphocytes; its biodistribution predominates in the spleen, thymus, and bone marrow. In addition, D-FAC is taken up at high levels by the intestine. We analyzed the regional specificity of uptake and cell types that mediate it. Methods: In mice, 3-dimensional isocontour regions of interest were drawn based on computed tomographic images to quantify intestinal signals from micro-positron emission tomography scans. To ascertain the cell type responsible, intestinal epithelium and immune cells were isolated and D-FAC uptake was analyzed in vitro. Mice deficient in mucosal homing (β7 integrin-/-), enteric microbiota (germ-free), or active for immune colitis (Gαi2-/- CD3+ transferred into Rag-/- recipients) were studied. Results: Strong uptake of D-FAC was detected throughout the intestine, with greatest signal per region of interest in the duodenum. Fractionation of intestinal cell types after in vivo uptake revealed that the signal was almost entirely from epithelial cells. Among resident immune cell types, CD4+ T cells showed the greatest per-cell and total uptake. D-FAC uptake increased in both intestinal and systemic lymphoid sites during colitis. Compared with fluorodeoxyglucose, increased uptake of D-FAC in the small and large intestine occurred at an earlier stage of disease development. Conclusions: Uptake of D-FAC is a prominent trait of normal mouse intestinal epithelial cells, which is useful for their noninvasive visualization by positron emission tomography. Increased uptake of D-FAC reflects the activity of the epithelium and lymphocytes, providing a unique early marker of intestinal inflammation.",
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AU - Nair-Gill, Evan

AU - Wei, Bo

AU - Chen, Ling

AU - Li, Xiaoxiao

AU - Riedinger, Mireille

AU - Campbell, Dean O.

AU - Wiltzius, Stephanie

AU - Satyamurthy, Nagichettiar

AU - Phelps, Michael E.

AU - Radu, Caius

AU - Witte, Owen N.

AU - Braun, Jonathan

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N2 - Background & Aims: Uptake of [18F]1-(2′-deoxy-2′-arabinofuranosyl)cytosine (D-FAC) is a trait of activated lymphocytes; its biodistribution predominates in the spleen, thymus, and bone marrow. In addition, D-FAC is taken up at high levels by the intestine. We analyzed the regional specificity of uptake and cell types that mediate it. Methods: In mice, 3-dimensional isocontour regions of interest were drawn based on computed tomographic images to quantify intestinal signals from micro-positron emission tomography scans. To ascertain the cell type responsible, intestinal epithelium and immune cells were isolated and D-FAC uptake was analyzed in vitro. Mice deficient in mucosal homing (β7 integrin-/-), enteric microbiota (germ-free), or active for immune colitis (Gαi2-/- CD3+ transferred into Rag-/- recipients) were studied. Results: Strong uptake of D-FAC was detected throughout the intestine, with greatest signal per region of interest in the duodenum. Fractionation of intestinal cell types after in vivo uptake revealed that the signal was almost entirely from epithelial cells. Among resident immune cell types, CD4+ T cells showed the greatest per-cell and total uptake. D-FAC uptake increased in both intestinal and systemic lymphoid sites during colitis. Compared with fluorodeoxyglucose, increased uptake of D-FAC in the small and large intestine occurred at an earlier stage of disease development. Conclusions: Uptake of D-FAC is a prominent trait of normal mouse intestinal epithelial cells, which is useful for their noninvasive visualization by positron emission tomography. Increased uptake of D-FAC reflects the activity of the epithelium and lymphocytes, providing a unique early marker of intestinal inflammation.

AB - Background & Aims: Uptake of [18F]1-(2′-deoxy-2′-arabinofuranosyl)cytosine (D-FAC) is a trait of activated lymphocytes; its biodistribution predominates in the spleen, thymus, and bone marrow. In addition, D-FAC is taken up at high levels by the intestine. We analyzed the regional specificity of uptake and cell types that mediate it. Methods: In mice, 3-dimensional isocontour regions of interest were drawn based on computed tomographic images to quantify intestinal signals from micro-positron emission tomography scans. To ascertain the cell type responsible, intestinal epithelium and immune cells were isolated and D-FAC uptake was analyzed in vitro. Mice deficient in mucosal homing (β7 integrin-/-), enteric microbiota (germ-free), or active for immune colitis (Gαi2-/- CD3+ transferred into Rag-/- recipients) were studied. Results: Strong uptake of D-FAC was detected throughout the intestine, with greatest signal per region of interest in the duodenum. Fractionation of intestinal cell types after in vivo uptake revealed that the signal was almost entirely from epithelial cells. Among resident immune cell types, CD4+ T cells showed the greatest per-cell and total uptake. D-FAC uptake increased in both intestinal and systemic lymphoid sites during colitis. Compared with fluorodeoxyglucose, increased uptake of D-FAC in the small and large intestine occurred at an earlier stage of disease development. Conclusions: Uptake of D-FAC is a prominent trait of normal mouse intestinal epithelial cells, which is useful for their noninvasive visualization by positron emission tomography. Increased uptake of D-FAC reflects the activity of the epithelium and lymphocytes, providing a unique early marker of intestinal inflammation.

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KW - Inflammatory bowel disease

KW - Positron emission tomography

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