PET and Macro- and Microautoradiographic Studies Combined with Immunohistochemistry for Monitoring Rat Intestinal Ulceration and Healing Processes

Abstract

18 F-FDG PET is used mainly in clinical settings for imaging focal cancer sites, but the usefulness of the modality in imaging gastrointestinal ulcers has not been established. We investigated whether PET can be used for noninvasive monitoring of indomethacin-induced small-intestine ulceration. Methods: Intestinal ulcers were induced in rats by subcutaneous administration of indomethacin. An 18 F-FDG PET scan was obtained at 1, 2, and 7 d after indomethacin administration. 18 F-FDG uptake in the small intestine was quantified by g-counting, and macro-and microautoradiographic studies were performed to determine the site of 18 F-FDG uptake in tissue and at the cellular level. Results: Ulcers observed in the intestine (mainly in the ileum) 1-4 d after indomethacin administration were most severe at 1 d after administration and were almost healed at day 7. The PET study showed increased 18 F-FDG uptake in the intestine correlating to the severity of ulceration, returning to the basal level on day 7. Ex vivo imaging and g-counting showed that these regions of high uptake corresponded to regions of ulceration. A microautoradiographic study combined with immunohistochemistry revealed heavy accumulation of 18 F-FDG in inflammatory cells containing peroxidase on day 1 and in cells forming granulation tissue (a-smooth muscle actin-positive myofibroblasts and ED2-positive macrophages) on days 2-4 in and around ulcers. Proliferating (Ki67-immunopositive) intestinal crypt cells were also densely labeled with 18 F-FDG in intact intestinal tissue taken from the indomethacin-treated and the control animals. Conclusion: Our experimental data suggest that 18 F-FDG PET may be useful for evaluating the occurrence of small-intestine ulcers. Ulceration could be visualized early by the prominent uptake of 18 F-FDG by inflammatory cells and by the formation of granulation tissue by cells in and around ulcers.

PET Imaging Analysis with 64Cu in Disulfiram Treatment for Aberrant Copper Biodistribution in Menkes Disease Mouse Model

“…In mice pretreated with D-penicillamine (100 mg/kg; Wako Pure Chemicals), D-penicillamine diluted with saline was injected subcutaneously. (29). Each sample was counted in a 1470 WIZARD automatic g counter (Wallac).…”

Autoradiography, MALDI-MS, and SIMS-MS Imaging in Pharmaceutical Discovery and Development

“…More recent work by Yamamoto et al (55) used MARG in combination with immunohistochemistry, macroautoradiography, and positron emission topography to examine intestinal ulceration and healing in the rat. They used 18 F-FDG to examine ulcerations in the small intestine of rats, which were induced using indomethacin.…”

Enzymatic synthesis of 2-deoxyglucose-containing maltooligosaccharides for tracing the location of glucose absorption from starch digestion

“…Thus, the 2-DG-6P accumulates in the small intestinal enterocyte cells (Burant & Bell, 1992;Olefsky, 1978). Due to this accumulative property in the cell, labeled 2-DG's (e.g., 14 C-, 3 H-, and 2-F-2-DG) are used to trace the location of glucose entry into a range of target cells using different types of imaging systems (Durham & Woolsey, 1985;Nedergaard & Astrup, 1986;Yamato, Kataoka, Mizuma, Wada, & Watanabe, 2009).…”