title: Myocardial uptake of 7'-(Z)-[(123)I]iodorotenone during vasodilator stress in dogs with critical coronary stenoses.
abstract: BACKGROUND
  There is a well-recognized need for a new generation of single photon emission computed tomography (SPECT) perfusion tracers with improved myocardial extraction over a wide flow range. Radiotracers that target complex I of the mitochondrial electron transport chain have been proposed as a new class of myocardial perfusion imaging agents. 7-(Z)-[(125)I]iodorotenone ((125)I-ZIROT) has demonstrated superior myocardial extraction and retention characteristics in rats and in isolated perfused rabbit hearts. We sought to fully characterize the biodistribution and myocardial extraction versus flow relationship of (123)I-ZIROT in an intact large-animal model.
  
  
  RESULTS
  The (123)I-ZIROT was administered during adenosine A(2A) agonist-induced hyperemia in 5 anesthetized dogs with critical left anterior descending (LAD) stenoses. When left circumflex (LCx) flow was maximal, (123)I-ZIROT and microspheres were coinjected and the dogs were euthanized 5 minutes later. (123)I-ZIROT biodistribution was evaluated in 2 additional dogs by in vivo planar imaging. At (123)I-ZIROT injection, transmural LAD flow was unchanged from baseline (mean±SEM, 0.90±0.22 versus 0.87±0.11 mL/[min · g]; P=0.92), whereas LCx zone flow increased significantly (mean±SEM, 3.25±0.51 versus 1.00±0.17 mL/[min · g]; P<0.05). Myocardial (123)I-ZIROT extraction tracked regional myocardial flow better than either thallium-201 or (99m)Tc-sestamibi from previous studies using a similar model. Furthermore, the (123)I-ZIROT LAD/LCx activity ratios by ex vivo imaging or well counting (mean±SEM, 0.42±0.08 and 0.45±0.1, respectively) only slightly underestimated the LAD/LCx microsphere flow ratio (0.32±0.09).
  
  
  CONCLUSIONS
  The ability of (123)I-ZIROT to more linearly track blood flow over a wide range makes it a promising new SPECT myocardial perfusion imaging agent with potential for improved coronary artery disease detection and better quantitative estimation of the severity of flow impairment.
authors.affiliation: Experimental Cardiology Laboratory, Cardiovascular Division, Department of Medicine, University of Virginia Health System, Charlottesville, VA 22908, USA.
authors.forename: Alexis
authors.initials: A
authors.lastname: Broisat
authors.forename: Mirta
authors.initials: M
authors.lastname: Ruiz
authors.forename: Norman C
authors.initials: NC
authors.lastname: Goodman
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hanrahan
authors.forename: Bryan W
authors.initials: BW
authors.lastname: Reutter
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Brennan
authors.forename: Mustafa
authors.initials: M
authors.lastname: Janabi
authors.forename: Saul
authors.initials: S
authors.lastname: Schaefer
authors.forename: Denny D
authors.initials: DD
authors.lastname: Watson
authors.forename: George A
authors.initials: GA
authors.lastname: Beller
authors.forename: Henry F
authors.initials: HF
authors.lastname: VanBrocklin
authors.forename: David K
authors.initials: DK
authors.lastname: Glover
mesh_terms: D058908:Adenosine A2 Receptor Agonists; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D023921:Coronary Stenosis / Q000000981:diagnostic imaging* / Q000503:physiopathology; D016638:Critical Illness; D004195:Disease Models, Animal; D004285:Dogs; D025401:Echocardiography, Stress; D006439:Hemodynamics / Q000502:physiology*; D007089:Image Enhancement / Q000379:methods; D007457:Iodine Radioisotopes; D008297:Male; D011897:Random Allocation; D012402:Rotenone / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D012680:Sensitivity and Specificity; D013794:Thallium Radioisotopes / Q000493:pharmacokinetics*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: C421170:7'-iodorotenone; D058908:Adenosine A2 Receptor Agonists; D007457:Iodine Radioisotopes; D013794:Thallium Radioisotopes; D012402:Rotenone