Epithelial uptake of [18F]1-(2'-deoxy-2'-arabinofuranosyl) cytosine indicates intestinal inflammation in mice.

Abstract

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. 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. 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. 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.