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Preclinical investigation of potential use of thymidine phosphorylase-targeting tracer for diagnosis of nonalcoholic steatohepatitis

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Title: Preclinical investigation of potential use of thymidine phosphorylase-targeting tracer for diagnosis of nonalcoholic steatohepatitis
Authors: Higashikawa, Kei Browse this author →KAKEN DB
Horiguchi, Sawako Browse this author
Tarisawa, Makoto Browse this author
Shibata, Yuki Browse this author
Ohkura, Kazue Browse this author →KAKEN DB
Yasui, Hironobu Browse this author →KAKEN DB
Takeda, Hiroshi Browse this author →KAKEN DB
Kuge, Yuji Browse this author →KAKEN DB
Keywords: NASH
Issue Date: Mar-2020
Publisher: Elsevier
Journal Title: Nuclear medicine and biology
Volume: 82–83
Start Page: 25
End Page: 32
Publisher DOI: 10.1016/j.nucmedbio.2019.12.006
Abstract: Introduction: Although liver biopsy is the gold standard for the diagnosis of nonalcoholic steatohepatitis (NASH), it has several problems including high invasiveness and sampling errors. Therefore, the development of alternative methods to overcome these disadvantages is strongly required. In this study, we evaluated the potential use of our tracer targeting thymidine phosphorylase (TYMP),5-[I-123]iodo-6-[(2-iminoimidazolidinyl)methylluracil ([I-123]IIMU) for the diagnosis of NASH. Methods: The mice used as the NASH model (hereafter, NASH mice) were prepared by feeding a methionine- and choline-deficient diet for 4 weeks. A control group was similarly given a control diet. The expression levels of the TYMP gene and protein in the liver were examined by real-time reverse-transcription polymerase chain reaction and western blot analyses. The localizations of [I-125]IIMU and the TYMP protein in the liver were examined by autoradiography and immunohistochemical staining, respectively. Finally, the mice were injected with [I-123] IIMU and single-photon emission tomography (SPECT) imaging was conducted. Results: The hepatic expression levels of TYMP were significantly lower in the NASH mice than in the control mice at both mRNA and protein levels, suggesting that a decrease in TYMP level could be an indicator of NASH. [I-125] IIMU was uniformly distributed in the liver of the control mice, whereas it showed a patchy distribution in that of the NASH mice. The localization of [ I-125]IIMU was visually consistent with that of the TYMP protein in the liver of the control and NASH mice. SPECT analysis indicated that the hepatic accumulation of [I-123]IIMU in the NASH mice was significantly lower than that in the control mice ISUV (g/ml): 4.14 +/- 0.87 (Control) vs 2.31 = 029 (NASH)]. Conclusions: [I-12(3)]IIMU may provide a noninvasive means for imaging TYMP expression in the liver and may be applicable to the diagnosis of NASH. (C) 2019 Published by Elsevier Inc.
Rights: © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
Type: article (author version)
Appears in Collections:アイソトープ総合センター (Central Institute of Isotope Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 久下 裕司

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