Thymidine phosphorylase imaging probe for differential diagnosis of metabolic dysfunction-associated steatohepatitis

Higashikawa, Kei; Uehara, Riho; Horiguchi, Sawako; Shibata, Yuki; Okubo, Naoto; Mizuno, Yuki; Yasui, Hironobu; Ohnishi, Shunsuke; Takeda, Hiroshi; Kuge, Yuji

Thymidine phosphorylase imaging probe for differential diagnosis of metabolic dysfunction-associated steatohepatitis

Higashikawa, Kei; Uehara, Riho; Horiguchi, Sawako et al.

Molecular imaging and biology, 2024, 26(6), 1036-1045

Permalink : https://hdl.handle.net/2115/97310

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アクセス権	open access
URI	https://hdl.handle.net/2115/97310
タイトル	Thymidine phosphorylase imaging probe for differential diagnosis of metabolic dysfunction-associated steatohepatitis
著者	Higashikawa, Kei ; Uehara, Riho ; Horiguchi, Sawako ; Shibata, Yuki ; Okubo, Naoto ; Mizuno, Yuki ; Yasui, Hironobu ; Ohnishi, Shunsuke ; Takeda, Hiroshi ; Kuge, Yuji
e-Rad_Researcher 10756878 著者名 Higashikawa, Kei
著者名 Uehara, Riho
著者名 Horiguchi, Sawako
著者名 Shibata, Yuki
著者名 Okubo, Naoto
著者名 Mizuno, Yuki
著者名 Yasui, Hironobu
著者名 Ohnishi, Shunsuke
著者名 Takeda, Hiroshi
e-Rad_Researcher 70321958 著者名 Kuge, Yuji
言語	英語
キーワード	Metabolic dysfunction-associated steatohepatitis (MASH)
	Non-alcoholic steatohepatitis (SS)
	Thymidine phosphorylase (TYMP)
	5-iodo-6-[(2-iminoimidazolidinyl)methyl]uracil (IIMU)
	Nuclear medicine imaging
発行日	2024-11-13
出版者	Springer
収録物名	Molecular imaging and biology
巻(号)	26(6)
ページ	1036-1045
抄録	Purpose Metabolic dysfunction-associated steatotic liver disease (MASLD) comprises simple steatosis (SS), which has a low risk of mortality, and metabolic dysfunction-associated steatohepatitis (MASH), which can progress to liver cirrhosis and hepatocellular carcinoma. Because differentiation between MASH and SS is the most important issue in the diagnosis of MASLD, the establishment of noninvasive diagnostic methods is urgently needed. In this study, we evaluated the potential of [123I]IIMU, a thymidine phosphorylase (TYMP) targeted SPECT imaging probe, for differential diagnosis of MASLD in a preclinical animal model. Procedures SS and MASH mice were prepared by feeding db/db mice with a standard diet and a methionine/choline-deficient diet, respectively. Control mice were prepared by feeding m/m mice with a standard diet. TYMP expression in the liver was evaluated by RT-PCR, western blotting, and immunohistochemistry. The biodistribution of [125I]IIMU in the three model mice was evaluated at 30 min post-injection. SPECT/CT imaging studies of the three model mice were performed 30 min after injection of [123I]IIMU. Results Hepatic TYMP expression level was the highest in the SS mice and the lowest in the MASH mice at both mRNA and protein levels. The immunohistochemistry experiment showed a patchy distribution of TYMP only in the liver of MASH mice. In the biodistribution study, the hepatic accumulation of [125I]IIMU was the highest in the SS mice and the lowest in the MASH mice. The SPECT/CT imaging study showed similar results to the biodistribution experiment. Conclusion Hepatic TYMP expression level may serve as a promising imaging biomarker for differential diagnosis of SS and MASH. SPECT imaging using [123I]IIMU potentially provides a novel noninvasive diagnostic method to differentiate MASH and SS.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1007/s11307-024-01964-4
PISSN	1536-1632
EISSN	1860-2002
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1007/s11307-024-01964-4