title: 4-[18F]-tetraphenylphosphonium as a PET tracer for myocardial mitochondrial membrane potential.
abstract: OBJECTIVE
  This study tested the hypothesis that 4-[(18)F]fluorophenyltriphenylphosphonium ((18)F-TPP) is useful for in vivo positron emission tomography (PET) measurement of mitochondrial membrane potential (ΔΨm). Its utility as a blood flow tracer also was evaluated.
  
  
  BACKGROUND
  Tetraphenylphosphonium is useful for in vitro measurement of ΔΨm. In vivo measurement of ΔΨm has potential value in the assessment of heart failure pathophysiology and therapy as well as assessment of myocardial viability and so may be a very useful clinical tool.
  
  
  METHODS
  Anesthetized swine (N = 6) with a balloon catheter in the left anterior descending coronary artery were studied. Microsphere measurements of myocardial blood flow (MBF) were made after balloon inflation (baseline) and ∼10 min after intravenous administration of adenosine and phenylephrine after which ∼10 mCi (18)F-TPP was injected intravenously and dynamic PET data acquisition obtained for 30 min. After the swine were killed, the hearts were sectioned for microsphere measurement of MBF and (18)F-TPP measured by well counter in these same samples. PET images provided whole blood and myocardial (18)F-TPP concentration for determination of ΔΨm by the Nernst equation, corrected for nonspecific (18)F-TPP binding. Microsphere MBF, absolute (ml/min/g) and relative, was compared with PET data (standard uptake value and K1).
  
  
  RESULTS
  Nonspecific binding of (18)F-TPP overestimated ΔΨm measured by -37 ± 4 mV (mean ± SD). Normal zone ΔΨm of ex vivo samples (-91 ± 11 mV; N = 52; sample weight, 1.07 ± 0.18 g) correlated strongly (R(2)= 0.93) with normal zone by PET (-81 ± 13 mV). Both ex vivo and PET normal zone ΔΨm, although somewhat lower, compared well with that reported for tritium labeled triphenylphosphonium in normal working Langendorff rat heart (-100 mV). Although the relative MBF by (18)F-TPP correlated strongly with relative microsphere MBF (R(2)= 0.83), there was no correlation between absolute MBF by (18)F-TPP and microsphere MBF.
  
  
  CONCLUSIONS
  (18)F-TPP is a promising tracer for noninvasive PET measurement of ΔΨm in living subjects. It is useful as well for assessment of relative but not absolute MBF.
authors.affiliation: Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA.
authors.forename: Gagandeep S
authors.initials: GS
authors.lastname: Gurm
authors.forename: Stephan B
authors.initials: SB
authors.lastname: Danik
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Shoup
authors.forename: Steven
authors.initials: S
authors.lastname: Weise
authors.forename: Kazue
authors.initials: K
authors.lastname: Takahashi
authors.forename: Shawna
authors.initials: S
authors.lastname: Laferrier
authors.forename: David R
authors.initials: DR
authors.lastname: Elmaleh
authors.forename: Henry
authors.initials: H
authors.lastname: Gewirtz
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging* / Q000503:physiopathology; D003326:Coronary Circulation; D004195:Disease Models, Animal; D006439:Hemodynamics; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008929:Mitochondria, Heart / Q000000981:diagnostic imaging* / Q000378:metabolism; D055414:Myocardial Perfusion Imaging / Q000379:methods*; D009206:Myocardium / Q000378:metabolism; D009861:Onium Compounds / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000378:metabolism; D010092:Oximetry; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000378:metabolism; D034421:Sus scrofa
chemical_list: D009861:Onium Compounds; D009943:Organophosphorus Compounds; D019275:Radiopharmaceuticals; C013289:tetraphenylphosphonium