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OtherBASIC SCIENCE INVESTIGATIONS

Dependence of Cardiac 11C-meta-Hydroxyephedrine Retention on Norepinephrine Transporter Density

David M. Raffel, Wei Chen, Phillip S. Sherman, David L. Gildersleeve and Yong-Woon Jung
Journal of Nuclear Medicine September 2006, 47 (9) 1490-1496;
David M. Raffel
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Wei Chen
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Phillip S. Sherman
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David L. Gildersleeve
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Yong-Woon Jung
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  • FIGURE 1. 
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    FIGURE 1. 

    Representative saturation binding assays for different 6-OHDA doses. Specific binding data are means ± SEM of triplicate determinations at each 3H-mazindol concentration. Solid lines are nonlinear regression fits of data to a 1-site binding model. For each assay, estimated values of Bmax and KD, and the associated uncertainties in those estimates, are shown.

  • FIGURE 2. 
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    FIGURE 2. 

    (A) Effect of 6-OHDA–induced denervation on cardiac NET density (Bmax). (B) Effect of 6-OHDA–induced denervation on cardiac 11C-HED uptake at 30 min. (C) Dependence of cardiac 11C-HED uptake at 30 min on NET density (Bmax).

  • FIGURE 3. 
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    FIGURE 3. 

    Proposed comprehensive compartmental model of cardiac HED kinetics. Arrow thicknesses indicate relative magnitudes of the rate constants. Cp = concentration in plasma; CE = concentration in extracellular space; Caxo = concentration in neuronal axoplasm; Cves = concentration in vesicles.

  • FIGURE 4. 
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    FIGURE 4. 

    Expected nonlinear relationship between HED retention and regional sympathetic nerve density in human heart, based on the comprehensive compartmental model shown in Figure 3.

Tables

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    TABLE 1

    Averages of NET Bmax, 3H-Mazindol Binding Affinity (KD), and HED Tissue Concentrations

    6-OHDA dose (mg/kg)nNET Bmax (fmol/mg protein)KD (nmol/L)HED concentration at 30 min (%ID/g)
    Whole heartLeft atriumRight atriumLeft ventricleRight ventricleBlood
    05388 ± 230.72 ± 0.072.89 ± 0.352.95 ± 0.362.60 ± 0.272.73 ± 0.343.51 ± 0.460.073 ± 0.006
    75266 ± 450.73 ± 0.142.14 ± 0.332.01 ± 0.522.25 ± 0.641.96 ± 0.342.73 ± 0.340.081 ± 0.011
    115167 ± 941.08 ± 0.321.18 ± 0.870.74 ± 0.461.35 ± 0.841.09 ± 0.801.54 ± 1.260.105 ± 0.013
    155181 ± 650.94 ± 0.241.33 ± 0.560.93 ± 0.761.34 ± 0.481.26 ± 0.561.65 ± 0.590.105 ± 0.011
    225100 ± 310.95 ± 0.480.76 ± 0.320.32 ± 0.090.56 ± 0.290.75 ± 0.320.90 ± 0.380.102 ± 0.009
    100531 ± 61.83 ± 0.910.22 ± 0.060.18 ± 0.050.22 ± 0.050.22 ± 0.060.22 ± 0.050.091 ± 0.023
    • Values are mean ± SD.

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    TABLE 2

    Averages of NET Bmax, KD, and HED Concentrations for Hearts with Comparable NET Densities

    NET Bmax range (fmol/mg protein)nNET Bmax (fmol/mg protein)KD (nmol/L)HED concentration at 30 min (%ID/g)
    Whole heartLeft atriumRight atriumLeft ventricleRight ventricleBlood
    ≥3505388 ± 230.72 ± 0.072.89 ± 0.352.95 ± 0.362.60 ± 0.272.73 ± 0.343.51 ± 0.460.073 ± 0.006
    300–3492320 ± 10.70 ± 0.112.59 ± 0.052.04 ± 1.002.53 ± 0.262.42 ± 0.083.28 ± 0.330.081 ± 0.002
    250–2994276 ± 160.74 ± 0.132.06 ± 0.182.03 ± 0.312.33 ± 0.361.89 ± 0.192.58 ± 0.370.082 ± 0.013
    200–2490————————
    150–1995177 ± 130.95 ± 0.231.42 ± 0.470.88 ± 0.421.42 ± 0.401.32 ± 0.451.86 ± 0.660.105 ± 0.013
    100–1496121 ± 190.99 ± 0.280.81 ± 0.220.41 ± 0.150.72 ± 0.360.78 ± 0.210.99 ± 0.300.104 ± 0.009
    50–99374 ± 81.16 ± 0.650.57 ± 0.320.31 ± 0.090.55 ± 0.290.55 ± 0.320.67 ± 0.380.109 ± 0.006
    0–49531 ± 61.83 ± 0.910.22 ± 0.060.18 ± 0.050.22 ± 0.050.22 ± 0.060.22 ± 0.050.091 ± 0.023
    • Values are mean ± SD.

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Journal of Nuclear Medicine: 47 (9)
Journal of Nuclear Medicine
Vol. 47, Issue 9
September 2006
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Dependence of Cardiac 11C-meta-Hydroxyephedrine Retention on Norepinephrine Transporter Density
David M. Raffel, Wei Chen, Phillip S. Sherman, David L. Gildersleeve, Yong-Woon Jung
Journal of Nuclear Medicine Sep 2006, 47 (9) 1490-1496;

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Dependence of Cardiac 11C-meta-Hydroxyephedrine Retention on Norepinephrine Transporter Density
David M. Raffel, Wei Chen, Phillip S. Sherman, David L. Gildersleeve, Yong-Woon Jung
Journal of Nuclear Medicine Sep 2006, 47 (9) 1490-1496;
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