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EJNMMI Research
Published in: EJNMMI Research 1/2018

Open Access 01-12-2018 | Original research

Sensitive and early detection of mitochondrial dysfunction in the liver of NASH model mice by PET imaging with 18F-BCPP-BF

Authors: Toshihiro Sakai, Hiroyuki Ohba, Shingo Nishiyama, Takeharu Kakiuchi, Osamu Inoue, Hideo Tsukada

Published in: EJNMMI Research | Issue 1/2018

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Abstract

Background

Nonalcoholic fatty liver disease is a common disorder that progresses from simple fatty liver (steatosis) to nonalcoholic steatohepatitis (NASH). It is thought that mitochondrial dysfunction plays a critical role in the progression of NASH. In this study, we developed a non-invasive method for early diagnosis and staging of NASH that directly measures mitochondrial complex-I (MC-I) activity in the liver of NASH model mice by positron emission tomography (PET) imaging using the novel tracer 2-tert-butyl-4-chloro-5-[6-(4-[18F]fluorobutoxy)-pyridin-3-ylmethoxy]-2H-pyridazin-3-one (18F-BCPP-BF). Liver uptake of 18F-BCPP-BF in NASH and age-matched control mice was measured as a standard uptake value over a period of 1 to 12 weeks. Histopathological evaluation of the liver tissue was performed by haematoxylin and eosin staining, and fibrosis was assessed by Masson’s trichrome staining.

Results

Significant mitochondrial dysfunction was detected as early as 1 week after commencing the diet, and MC-I activity in the liver measured by PET was reduced by > 50% relative to that in age-matched control mice after 6 weeks. Liver uptake of 18F-BCPP-BF was low throughout the 12-week experimental period. Histopathological examination revealed that steatosis, inflammation, and ballooning progressed from 1 to 6 weeks, with fibrosis observed from 6 to 12 weeks.

Conclusions

PET scans and histopathological analysis revealed that mitochondrial dysfunction in the liver contributed to the progression of NASH. PET imaging with 18F-BCPP-BF is a useful tool for detecting NASH at early stages and for monitoring therapeutic response.
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Metadata
Title
Sensitive and early detection of mitochondrial dysfunction in the liver of NASH model mice by PET imaging with 18F-BCPP-BF
Authors
Toshihiro Sakai
Hiroyuki Ohba
Shingo Nishiyama
Takeharu Kakiuchi
Osamu Inoue
Hideo Tsukada
Publication date
01-12-2018
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2018
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/s13550-018-0420-6

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