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

胸苷磷酸化酶靶向示踪剂在非酒精性脂肪性肝炎诊断中的潜在应用临床前研究

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作者:Kei Higashikawa, Sawako Horiguchi, Makoto Tarisawa, Yuki Shibata, Kazue Ohkura, Hironobu Yasui, Hiroshi Takeda, Yuji Kuge

Conclusions

[123I]IIMU may provide a noninvasive means for imaging TYMP expression in the liver and may be applicable to 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 [125I]IIMU and the TYMP protein in the liver were examined by autoradiography and immunohistochemical staining, respectively. Finally, the mice were injected with [123I]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. [125I]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 [125I]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 [123I]IIMU in the NASH mice was significantly lower than that in the control mice [SUV (g/ml): 4.14 ± 0.87 (Control) vs 2.31 ± 0.29 (NASH)]. Conclusions: [123I]IIMU may provide a noninvasive means for imaging TYMP expression in the liver and may be applicable to the diagnosis of NASH.

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