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

¹ Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, Japan; and ² RIKEN Center for Molecular Imaging Science, Chuo-ku, Kobe, Hyogo, Japan

Correspondence: For correspondence or reprints contact: Yasuyoshi Watanabe, Department of Physiology, Osaka City University Graduate School of Medicine, 1-4-3, Asahimachi, Abeno-ku, Osaka 545-8585, Japan. E-mail: yywata{at}riken.jp

¹⁸F-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 ¹⁸F-FDG PET scan was obtained at 1, 2, and 7 d after indomethacin administration. ¹⁸F-FDG uptake in the small intestine was quantified by -counting, and macro- and microautoradiographic studies were performed to determine the site of ¹⁸F-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 ¹⁸F-FDG uptake in the intestine correlating to the severity of ulceration, returning to the basal level on day 7. Ex vivo imaging and -counting showed that these regions of high uptake corresponded to regions of ulceration. A microautoradiographic study combined with immunohistochemistry revealed heavy accumulation of ¹⁸F-FDG in inflammatory cells containing peroxidase on day 1 and in cells forming granulation tissue (-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 ¹⁸F-FDG in intact intestinal tissue taken from the indomethacin-treated and the control animals. Conclusion: Our experimental data suggest that ¹⁸F-FDG PET may be useful for evaluating the occurrence of small-intestine ulcers. Ulceration could be visualized early by the prominent uptake of ¹⁸F-FDG by inflammatory cells and by the formation of granulation tissue by cells in and around ulcers.

Key Words: gastroenterology • molecular imaging • animal imaging • ¹⁸F-FDG • PET • indomethacin • intestinal ulceration • microautoradiography

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