Myocardial uptake of 7′-(Z)-[ 123I]iodorotenone during vasodilator stress in dogs with critical coronary stenoses

Alexis Broisat, Mirta Ruiz, Norman C. Goodman, Stephen M. Hanrahan, Bryan W. Reutter, Kathleen M. Brennan, Mustafa Janabi, Saul Schaefer, Denny D. Watson, George A. Beller, Henry F. VanBrocklin, David K. Glover

Research output: Contribution to journalArticle

6 Scopus citations

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)-[ 125I]iodorotenone ( 125I-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 123I-ZIROT in an intact large-animal model. Methods and Results-The 123I-ZIROT was administered during adenosine A 2Aagonist-induced hyperemia in 5 anesthetized dogs with critical left anterior descending (LAD) stenoses. When left circumflex (LCx) flow was maximal, 123I-ZIROT and microspheres were coinjected and the dogs were euthanized 5 minutes later. 123I-ZIROT biodistribution was evaluated in 2 additional dogs by in vivo planar imaging. At 123I-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 123I-ZIROT extraction tracked regional myocardial flow better than either thallium-201 or 99mTc-sestamibi from previous studies using a similar model. Furthermore, the 123I-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 123I-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.

Original languageEnglish (US)
Pages (from-to)685-692
Number of pages8
JournalCirculation: Cardiovascular Imaging
Volume4
Issue number6
DOIs
StatePublished - Nov 2011

Keywords

  • Coronary artery disease
  • Diagnosis
  • Myocardial perfusion imaging
  • Radioisotope

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Radiology Nuclear Medicine and imaging

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    Broisat, A., Ruiz, M., Goodman, N. C., Hanrahan, S. M., Reutter, B. W., Brennan, K. M., Janabi, M., Schaefer, S., Watson, D. D., Beller, G. A., VanBrocklin, H. F., & Glover, D. K. (2011). Myocardial uptake of 7′-(Z)-[ 123I]iodorotenone during vasodilator stress in dogs with critical coronary stenoses. Circulation: Cardiovascular Imaging, 4(6), 685-692. https://doi.org/10.1161/CIRCIMAGING.110.961763