title: Effects of acetaminophen on mitochondrial complex I activity in the rat liver and kidney: a PET study with18F-BCPP-BF.
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 of18F-BCPP-BF were assessed in rats using high-resolution animal PET in vivo. The binding specificity of18F-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 of18F-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 of18F-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 that18F-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.
authors.affiliation: Central Research Laboratory, Hamamatsu Photonics K.K., 5000 Hirakuchi, Hamamatsu, Shizuoka, 434-8601, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ohba
authors.affiliation: Central Research Laboratory, Hamamatsu Photonics K.K., 5000 Hirakuchi, Hamamatsu, Shizuoka, 434-8601, Japan.
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Kanazawa
authors.affiliation: Central Research Laboratory, Hamamatsu Photonics K.K., 5000 Hirakuchi, Hamamatsu, Shizuoka, 434-8601, Japan.
authors.forename: Takeharu
authors.initials: T
authors.lastname: Kakiuchi
authors.affiliation: Central Research Laboratory, Hamamatsu Photonics K.K., 5000 Hirakuchi, Hamamatsu, Shizuoka, 434-8601, Japan. tsukada@crl.hpk.co.jp.
authors.forename: Hideo
authors.identifier: http://orcid.org/0000-0002-8574-293X
authors.initials: H
authors.lastname: Tsukada
keywords: Acetaminophen; Hepatitis; Mitochondria complex I; Nephritis; PET