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EJNMMI Research
Published in: EJNMMI Research 1/2016

Open Access 01-12-2016 | Original research

Effects of acetaminophen on mitochondrial complex I activity in the rat liver and kidney: a PET study with 18F-BCPP-BF

Authors: Hiroyuki Ohba, Masakatsu Kanazawa, Takeharu Kakiuchi, Hideo Tsukada

Published in: EJNMMI Research | Issue 1/2016

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Abstract

Background

In the present study, 2-tert-butyl-4-chloro-5-[6-(4-18F-fluorobutoxy)-pyridin-3-ylmethoxy]-2H-pyridazin-3-one (18F-BCPP-BF), a PET probe for mitochondrial complex I (MC-I), was used to validate whether MC-I is a useful biomarker for detecting acetaminophen-induced dysfunctions in the liver and kidney.
The kinetic and distribution of 18F-BCPP-BF were assessed in rats using high-resolution animal PET in vivo. The binding specificity of 18F-BCPP-BF to MC-I in the liver and kidney was confirmed by the pre-administration of rotenone, a specific MC-I inhibitor. The effects of acetaminophen on MC-I activity were assessed 2 and 24 h after the administration of vehicle or acetaminophen at a dose of 100 or 300 mg/kg. Biochemical parameters in plasma and urine were assessed 2, 6, and 24 h after the administration of vehicle or acetaminophen.

Results

The uptake of 18F-BCPP-BF by the liver and kidney was significantly inhibited by the pre-administration of rotenone. Two and more hours after the administration of acetaminophen, the uptake of 18F-BCPP-BF was dose-dependently reduced in the liver, even at 100 mg/kg, and in the kidney at 300 mg/kg, whereas biological parameters started to be affected 6 h or later at doses of 300 mg/kg.

Conclusions

The present study demonstrated that 18F-BCPP-BF has potential as a PET probe for the quantitative imaging of hepatic and renal dysfunction as impaired MC-I activity in the early phase of the treatment for an overdose of acetaminophen in the living body with PET.
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Metadata
Title
Effects of acetaminophen on mitochondrial complex I activity in the rat liver and kidney: a PET study with 18F-BCPP-BF
Authors
Hiroyuki Ohba
Masakatsu Kanazawa
Takeharu Kakiuchi
Hideo Tsukada
Publication date
01-12-2016
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2016
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/s13550-016-0241-4

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