title: Exploration of target molecules for molecular imaging of inflammatory bowel disease.
abstract: Molecular imaging technology is a powerful tool for the diagnosis of inflammatory bowel disease (IBD) and the efficacy evaluation of various drug therapies for it. However, it is difficult to elucidate directly the relationships between the responsible molecules and IBD using existing probes. Therefore, the development of an alternative probe that is able to elucidate the pathogenic mechanism and provide information on the appropriate guidelines for treatment is earnestly awaited. In this study, we investigated pathognomonic molecules in the intestines of model mice. The accumulation of fluorine-18 fluorodeoxyglucose ((18)F-FDG) in the inflamed area of the intestines of dextran sulfate sodium (DSS)- or indomethacin (IND)-induced IBD model mice was measured by positron emission tomography (PET) and autoradiography to confirm the inflamed area. The results suggested that the inflammation was selectively induced in the colons of mice by the administration of DSS, whereas it was induced mainly in the ilea and the proximal colons of mice by the administration of IND. To explore attractive target molecules for the molecular imaging of IBD, we evaluated the gene expression levels of cytokines and cytokine receptors in the inflamed area of the intestines of both model mice. We found that the expression levels of cytokines and cytokine receptors were significantly increased during the progression of IBD, whereas the expression levels were decreased as the mucosa began to heal. In particular, the expression levels of these molecules had already changed before the symptoms of IBD appeared. In addition, the alterations of cytokine and cytokine receptor expression levels indicated differences in the expression pattern depending on the pathogenic mechanism or the region of inflammation (e.g., TNF-α). Our results suggest that these cytokines or cytokine receptors participate in the pathogenesis of IBD and are valuable biomarkers for the detection of the different circumstances underlying inflammation by the molecular imaging method. Finally, the development of an imaging probe for our target molecules is expected to improve our understanding of the inflammatory conditions of IBD.
authors.affiliation: Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Higashikawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Akada
authors.forename: Katsuharu
authors.initials: K
authors.lastname: Yagi
authors.forename: Keiko
authors.initials: K
authors.lastname: Watanabe
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Kamino
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Kanayama
authors.forename: Makoto
authors.initials: M
authors.lastname: Hiromura
authors.forename: Shuichi
authors.initials: S
authors.lastname: Enomoto
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D003106:Colon / Q000187:drug effects*; D016207:Cytokines / Q000032:analysis / Q000378:metabolism*; D016264:Dextran Sulfate / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D019788:Fluorodeoxyglucose F18; D007213:Indomethacin / Q000494:pharmacology*; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced* / Q000175:diagnosis*; D051379:Mice; D008807:Mice, Inbred BALB C; D049268:Positron-Emission Tomography; D018121:Receptors, Cytokine / Q000032:analysis / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018121:Receptors, Cytokine; D019788:Fluorodeoxyglucose F18; D016264:Dextran Sulfate; D007213:Indomethacin