Molecular Imaging of Murine Intestinal Inflammation With 2-Deoxy-2-[18F]Fluoro-d-Glucose and Positron Emission Tomography

Abstract

2-Deoxy-2-[(18)F]fluoro-d-glucose (FDG) uptake by positron emission tomography (PET), a measure of glucose transporter activity, has been used to detect mucosal inflammation. However, there is limited understanding of the biologic basis of mucosal FDG uptake. A contrast-based computed tomographic isocontour method was developed to identify intestinal anatomic regions, and FDG uptake was integrated over these regions to achieve reproducible quantification during longitudinal assessment of individual mice. Intestinal FDG uptake was compared with histologic scores and with glucose transporter 1 levels in mucosal immune cells by flow cytometry. Intestinal FDG uptake quantitatively correlated with disease activity in mild (C3H/HeJ.IL-10(-/-)) and severe (129.Galphai2(-/-), CD4(+) CD45RB(high), and Galphai2(-/-) CD3(+) transfer) murine colitis models at all time points examined (P < .05) and was sufficiently sensitive to detect preclinical inflammation. FDG uptake was correlated by flow cytometric detection of glucose transporter 1 levels in mucosal CD4(+) T lymphocyte but not other intestinal immune cell types. CD4(+) T-cell transfer in vivo confirmed that mucosal FDG uptake was associated with the activated but not quiescent state. When intestinal inflammation was increased by treatment with piroxicam and decreased with anti-TL1A treatment, FDG uptake was correspondingly altered. This study clarifies the cellular basis of FDG signal in intestinal inflammation and introduces computed tomographic isocontour analysis of FDG-PET imaging for standardized quantitation of immune colitis.