title: [(11)C]-Acetoacetate PET imaging: a potential early marker for cardiac heart failure.
abstract: The ketone body acetoacetate could be used as an alternate nutrient for the heart, and it also has the potential to improve cardiac function in an ischemic-reperfusion model or reduce the mitochondrial production of oxidative stress involved in cardiotoxicity. In this study, [(11)C]-acetoacetate was investigated as an early marker of intracellular damage in heart failure.
  
  
  METHODS
  A rat cardiotoxicity heart failure model was induced by doxorubicin, Dox(+). [(14)C]-Acetoacetate, a non-positron (β-) emitting radiotracer, was used to characterize the arterial blood input function and myocardial mitochondrial uptake. Afterward, [(11)C]-acetoacetate (β+) myocardial PET images were obtained for kinetic analysis and heart function assessment in control Dox(-) (n=15) and treated Dox(+) (n=6) rats. The uptake rate (K1) and myocardial clearance rate (k2or kmono) were extracted.
  
  
  RESULTS
  [(14)C]-Acetoacetate in the blood was increased in Dox(+), from 2 min post-injection until the last withdrawal point when the heart was harvested, as well as the uptake in the heart and myocardial mitochondria (unpaired t-test, p <0.05). PET kinetic analysis of [(11)C]-acetoacetate showed that rate constants K1, k2 and kmono were decreased in Dox(+) (p <0.05) combined with a reduction of 24% of the left ventricular ejection fraction (p <0.001).
  
  
  CONCLUSIONS
  Radioactive acetoacetate ex vivo analysis [(14)C], and in vivo kinetic [(11)C] studies provided evidence that [(11)C]-acetoacetate can assess heart failure Dox(+). Contrary to myocardial flow reserve (rest-stress protocol), [(11)C]-acetoacetate can be used to assess reduced kinetic rate constants without requirement of hyperemic stress response. The proposed [(11)C]-acetoacetate cardiac radiotracer in the investigation of heart disease is novel and paves the way to a potential role for [(11)C]-acetoacetate in cardiac pathophysiology.
authors.affiliation: Sherbrooke Molecular Imaging Center of CRCHUS, Department of Nuclear Medicine and Radiobiology, Université de Sherbrooke, Sherbrooke, QC, Canada. Electronic address: Etienne.Croteau@USherbrooke.ca.
authors.forename: Etienne
authors.initials: E
authors.lastname: Croteau
authors.affiliation: Sherbrooke Molecular Imaging Center of CRCHUS, Department of Nuclear Medicine and Radiobiology, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Tremblay
authors.affiliation: Sherbrooke Molecular Imaging Center of CRCHUS, Department of Nuclear Medicine and Radiobiology, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Gascon
authors.affiliation: Sherbrooke Molecular Imaging Center of CRCHUS, Department of Nuclear Medicine and Radiobiology, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Véronique
authors.initials: V
authors.lastname: Dumulon-Perreault
authors.affiliation: Department of Medicine, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Sébastien M
authors.initials: SM
authors.lastname: Labbé
authors.affiliation: Sherbrooke Molecular Imaging Center of CRCHUS, Department of Nuclear Medicine and Radiobiology, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Jacques A
authors.initials: JA
authors.lastname: Rousseau
authors.affiliation: Research Center on Aging, Université de Sherbrooke, Sherbrooke, QC, Canada; Department of Medicine, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Cunnane
authors.affiliation: Department of Medicine, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: André C
authors.initials: AC
authors.lastname: Carpentier
authors.affiliation: Division of Nuclear Medicine, Department of Radiology, University of British Columbia, Vancouver, BC, Canada.
authors.forename: François
authors.initials: F
authors.lastname: Bénard
authors.affiliation: Sherbrooke Molecular Imaging Center of CRCHUS, Department of Nuclear Medicine and Radiobiology, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Roger
authors.initials: R
authors.lastname: Lecomte
mesh_terms: D000090:Acetoacetates / Q000097:blood / Q000493:pharmacokinetics; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D015415:Biomarkers / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D004317:Doxorubicin / Q000633:toxicity; D006333:Heart Failure / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000378:metabolism; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution; D016277:Ventricular Function, Left
chemical_list: D000090:Acetoacetates; D000903:Antibiotics, Antineoplastic; D015415:Biomarkers; D002250:Carbon Radioisotopes; C016635:acetoacetic acid; D004317:Doxorubicin
keywords: Acetoacetate; Cardiotoxicity; Doxorubicin; Heart failure; Ketone bodies; Kinetic analysis