PET and Macro- and Microautoradiographic Studies Combined with Immunohistochemistry for Monitoring Rat Intestinal Ulceration and Healing Processes
PET and Macro- and Microautoradiographic Studies Combined with Immunohistochemistry for Monitoring Rat Intestinal Ulceration and Healing Processes
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DOI：
10.2967/jnumed.108.057943
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发表时间：
2009-02
影响因子：
9.3
通讯作者：
M. Yamato;Y. Kataoka;H. Mizuma;Yasuhiro Wada;Yasuyoshi Watanabe
中科院分区：
文献类型：
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作者：
M. Yamato;Y. Kataoka;H. Mizuma;Yasuhiro Wada;Yasuyoshi Watanabe
18F-FDG PET主要用于临床对局灶性癌症部位的成像，但对胃肠道溃疡成像的有用性尚未确定。我们研究PET是否可以用于无创监测消炎痛引起的小肠溃疡。方法：用吲哚美辛皮下注射诱导大鼠肠道溃疡。给予吲哚美辛后1、2和7 d进行18F-FDG PET扫描。采用γ-计数法定量测定小鼠小肠内18F-FDG的摄取，并进行宏观和微观放射自显像研究，以确定组织和细胞水平上18F-FDG的摄取位置。结果：吲哚美辛给药后1 ~ 4 d出现的肠道溃疡（以回肠溃疡为主）在给药后1 d最为严重，第7天基本愈合。PET研究显示，肠道中18F-FDG的摄取增加与溃疡的严重程度相关，在第7天恢复到基础水平。离体成像和γ-计数显示，这些高摄取区域与溃疡区域相对应。显微放射自显像结合免疫组织化学显示，在第1天，18F-FDG在含有过氧化物酶的炎症细胞中大量积累，在第2-4天，在溃疡及其周围形成肉芽组织的细胞（α-平滑肌肌动蛋白阳性的肌成纤维细胞和ed2阳性的巨噬细胞）中大量积累。在吲哚美辛处理和对照动物的完整肠组织中，增殖的（ki67免疫阳性）肠隐窝细胞也被18F-FDG密集标记。结论：我们的实验数据表明，18F-FDG PET可能有助于评估小肠溃疡的发生。通过炎症细胞对18F-FDG的显著摄取以及溃疡内和周围细胞形成肉芽组织，可以早期观察到溃疡。
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 γ-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 γ-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 (α-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.