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Research ArticleBasic Science Investigations

Flow-Dependent Uptake of 123I-CMICE-013, a Novel SPECT Perfusion Agent, Compared with Standard Tracers

R. Glenn Wells, Lihui Wei, Julia Petryk, Yin Duan, Brian Marvin, Rachel Timmins, Karen Soueidan, Pasan Fernando, Corinne Bensimon and Terrence D. Ruddy
Journal of Nuclear Medicine May 2015, 56 (5) 764-770; DOI: https://doi.org/10.2967/jnumed.114.151563
R. Glenn Wells
1Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
2Canadian Molecular Imaging Center of Excellence (CMICE), University of Ottawa Heart Institute, Ottawa, Ontario, Canada; and
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Lihui Wei
2Canadian Molecular Imaging Center of Excellence (CMICE), University of Ottawa Heart Institute, Ottawa, Ontario, Canada; and
3Nordion Inc., Ottawa, Ontario, Canada
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Julia Petryk
1Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
2Canadian Molecular Imaging Center of Excellence (CMICE), University of Ottawa Heart Institute, Ottawa, Ontario, Canada; and
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Yin Duan
2Canadian Molecular Imaging Center of Excellence (CMICE), University of Ottawa Heart Institute, Ottawa, Ontario, Canada; and
3Nordion Inc., Ottawa, Ontario, Canada
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Brian Marvin
1Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
2Canadian Molecular Imaging Center of Excellence (CMICE), University of Ottawa Heart Institute, Ottawa, Ontario, Canada; and
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Rachel Timmins
1Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
2Canadian Molecular Imaging Center of Excellence (CMICE), University of Ottawa Heart Institute, Ottawa, Ontario, Canada; and
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Karen Soueidan
1Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
2Canadian Molecular Imaging Center of Excellence (CMICE), University of Ottawa Heart Institute, Ottawa, Ontario, Canada; and
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Pasan Fernando
2Canadian Molecular Imaging Center of Excellence (CMICE), University of Ottawa Heart Institute, Ottawa, Ontario, Canada; and
3Nordion Inc., Ottawa, Ontario, Canada
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Corinne Bensimon
2Canadian Molecular Imaging Center of Excellence (CMICE), University of Ottawa Heart Institute, Ottawa, Ontario, Canada; and
2Canadian Molecular Imaging Center of Excellence (CMICE), University of Ottawa Heart Institute, Ottawa, Ontario, Canada; and
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Terrence D. Ruddy
1Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
2Canadian Molecular Imaging Center of Excellence (CMICE), University of Ottawa Heart Institute, Ottawa, Ontario, Canada; and
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  • FIGURE 1.
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    FIGURE 1.

    Blood time–activity curve for CMICE-013 based on counts from volume of interest in left ventricle. Time–activity curves do not go to zero at late times because of limited spatial resolution of SPECT and consequent spill-in from tracer in myocardial wall.

  • FIGURE 2.
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    FIGURE 2.

    Representative CMICE-013 images of porcine model of stress-induced myocardial ischemia showing stress (top) and rest (bottom) from 15–30 min after injection. Images are central slices in transverse (A and D), coronal (B and E), and sagittal (C and F) views. Images show good contrast between heart and surrounding tissues, except for liver for which contrast is similar to that of standard SPECT tracers.

  • FIGURE 3.
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    FIGURE 3.

    Ratios of maximum uptake in heart, compared with liver and lung at rest (A) and stress (B) for each of the tracers studied.

  • FIGURE 4.
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    FIGURE 4.

    Representative CMICE-013 images of heart. Images are shown at rest and stress (both 15 min after injection) for short axis (top) and vertical long axis (bottom). Images show good uniformity at rest and clear definition of the occluded region during stress.

  • FIGURE 5.
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    FIGURE 5.

    Tracer uptake versus microsphere flow values for each tissue sample from individual animals with CMICE-013 (A), 99mTc-tetrofosmin (B), 99mTc-sestamibi (C), and 201Tl (D). Fit to Equation 2 is shown as solid line for each dataset, with 95% confidence interval on fit represented by dotted lines. Fitted curves to combined data are replotted separately for clarity (E) along with curve derived from previously reported data for 123I-iodorotenone (ZIROT) (3) as described in supplemental materials. n = normal pigs; i = ischemic pigs.

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    TABLE 1

    Heart Rate and Systolic Blood Pressure for Animals at Rest and Stress

    RestStress
    TracerHeart rate (bpm)Systolic blood pressure (mm Hg)Heart rate (bpm)Systolic blood pressure (mm Hg)
    CMICE-013 (n = 10)82 ± 1266 ± 1082 ± 1059 ± 4
    Tetrofosmin (n = 9)84 ± 871 ± 886 ± 563 ± 9
    Sestamibi (n = 5)83 ± 1166 ± 1883 ± 1460 ± 16
    201Tl (n = 8)88 ± 1169 ± 1192 ± 860 ± 8
    • bpm = beats per minute.

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    TABLE 2

    Left Ventricular Heart Uptake (%ID/g × 70 g*) at Selected Microsphere Flow Values

    Microsphere flow (mL/min/g)†
    Tracer0.9‡1.52.03.04.0
    CMICE-0131.82.12.42.93.5
    Tetrofosmin1.1§1.1§1.2§1.2§1.3§
    Sestamibi1.4§1.6§1.7§1.8§1.9§
    201Tl1.2§1.3§1.5§1.8§2.1§
    • ↵* Heart weight used (70 g) is average left ventricle weight of pig hearts in this study.

    • ↵† Flow values based on fit for aggregate data to Equation 2.

    • ↵‡ 0.9 mL/min/g is average pig resting microsphere flow.

    • ↵§ Significantly different from CMICE-013 (P < 0.05).

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Journal of Nuclear Medicine: 56 (5)
Journal of Nuclear Medicine
Vol. 56, Issue 5
May 1, 2015
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Flow-Dependent Uptake of 123I-CMICE-013, a Novel SPECT Perfusion Agent, Compared with Standard Tracers
R. Glenn Wells, Lihui Wei, Julia Petryk, Yin Duan, Brian Marvin, Rachel Timmins, Karen Soueidan, Pasan Fernando, Corinne Bensimon, Terrence D. Ruddy
Journal of Nuclear Medicine May 2015, 56 (5) 764-770; DOI: 10.2967/jnumed.114.151563

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Flow-Dependent Uptake of 123I-CMICE-013, a Novel SPECT Perfusion Agent, Compared with Standard Tracers
R. Glenn Wells, Lihui Wei, Julia Petryk, Yin Duan, Brian Marvin, Rachel Timmins, Karen Soueidan, Pasan Fernando, Corinne Bensimon, Terrence D. Ruddy
Journal of Nuclear Medicine May 2015, 56 (5) 764-770; DOI: 10.2967/jnumed.114.151563
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Keywords

  • 123I-CMICE-013
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