PET and macro- and microautoradiographic studies combined with immunohistochemistry for monitoring rat intestinal ulceration and healing processes.
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 gamma-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 gamma-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 (alpha-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.


CONCLUSIONS
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.
Yamato
Masanori
M
Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Kataoka
Yosky
Y
Mizuma
Hiroshi
H
Wada
Yasuhiro
Y
Watanabe
Yasuyoshi
Y
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity; D001345:Autoradiography / Q000379:methods*; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D007150:Immunohistochemistry; D007213:Indomethacin / Q000633:toxicity; D007410:Intestinal Diseases / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D011859:Radiography; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D014456:Ulcer / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D009195:Peroxidase; D007213:Indomethacin