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 language | English (US) |
|---|---|
| Pages (from-to) | 1266-1275 |
| Number of pages | 10 |
| Journal | Gastroenterology |
| Volume | 138 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 2010 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Epithelial Uptake of [18F]1-(2′-Deoxy-2′-Arabinofuranosyl) Cytosine Indicates Intestinal Inflammation in Mice
AU - Brewer, Sarah
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
PY - 2010/4
Y1 - 2010/4
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.
KW - Cytosine nucleoside
KW - Fluorodeoxyglucose
KW - Inflammatory bowel disease
KW - Positron emission tomography
UR - http://www.scopus.com/inward/record.url?scp=77949838303&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77949838303&partnerID=8YFLogxK
U2 - 10.1053/j.gastro.2010.01.003
DO - 10.1053/j.gastro.2010.01.003
M3 - Article
C2 - 20080095
AN - SCOPUS:77949838303
VL - 138
SP - 1266
EP - 1275
JO - Gastroenterology
JF - Gastroenterology
SN - 0016-5085
IS - 4
ER -