Epithelial uptake of [18F]1-(2'-deoxy-2'-arabinofuranosyl) cytosine indicates intestinal inflammation in mice.
OBJECTIVE
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 (beta7 integrin-/-), enteric microbiota (germ-free), or active for immune colitis (G alpha i2-/- 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.
Brewer
Sarah
S
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California 90095-1732, USA.
Nair-Gill
Evan
E
Wei
Bo
B
Chen
Ling
L
Li
Xiaoxiao
X
Riedinger
Mireille
M
Campbell
Dean O
DO
Wiltzius
Stephanie
S
Satyamurthy
Nagichettiar
N
Phelps
Michael E
ME
Radu
Caius
C
Witte
Owen N
ON
Braun
Jonathan
J
D000818:Animals; D017209:Apoptosis; D003092:Colitis / Q000000981:diagnostic imaging*; D003561:Cytarabine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004386:Duodenum / Q000378:metabolism; D005260:Female; D019788:Fluorodeoxyglucose F18; D005856:Germ-Free Life; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D014018:Tissue Distribution
C548736:(18F)1-(2'-deoxy-2'-arabinofuranosyl)cytosine; D019275:Radiopharmaceuticals; D003561:Cytarabine; D019788:Fluorodeoxyglucose F18