OtherBasic Science Investigations

Quantitative Analysis of (−)-N-11C-Propyl-Norapomorphine In Vivo Binding in Nonhuman Primates

Dah-Ren Hwang, Rajesh Narendran, Yiyun Huang, Mark Slifstein, Peter S. Talbot, Yasuhiko Sudo, Bart N. Van Berckel, Lawrence S. Kegeles, Diana Martinez and Marc Laruelle
Journal of Nuclear Medicine February 2004, 45 (2) 338-346;

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    Mean ± SD fraction of plasma activity corresponding to the parent compound over time, after injection of 11C-NPA in baboons (n = 8).

  • FIGURE 2.
    FIGURE 2.

    Plasma 11C-NPA measurements in a typical experiment. ○ = total plasma activities; • = activities corresponding to unmetabolized 11C-NPA. Lines are values fitted to a sum of 3 exponentials.

  • FIGURE 3.
    FIGURE 3.

    Voxelwise V3″ map from a study (A) with coregistered MRI (B) of corresponding slices. Transaxial, coronal, and sagittal views are shown (left to right), all at the level of the striatum. These images were created by deriving VT in each voxel with kinetic analysis (1TCM) and applying Equation 3 on each voxel. Colors were scaled to V3″ values (0–2.8). Kinetic analysis was performed using a basis function approach (27) in the MATLAB environment on a 1.2-GHz personal computer running the Linux operating system and completed in approximately 15 min per brain.

  • FIGURE 4.
    FIGURE 4.

    Time-activity curves in cerebellum (○) and striatum (•) after injection of 11C-NPA. Points are measured values. Lines are values fitted to a 1TCM.

  • FIGURE 5.
    FIGURE 5.

    Relationship between scan duration and estimates of striatum V3″ by kinetic analysis. For each scan duration, estimated V3″ values were expressed in percentages of the value derived with the complete dataset (90 min). Each point is the average and SD of the 8 datasets. Decreasing the duration of scanning time from 90 to 30 min would induce only small biases and errors (<10%) on the estimates of V3″.

Tables

  • TABLE 1

    11C-NPA Peripheral Parameters*

    Baboonf1Vbol (L)CL (L/h)
    A5.0% ± 0.9%3.5 ± 0.530 ± 7
    B4.8% ± 0.6%3.1 ± 0.129 ± 5
    Average4.9% ± 0.1%3.3 ± 0.329 ± 1

    • ↵* Values are mean ± SD; n = 4 per baboon.

  • TABLE 2

    Comparison of Compartment Models for 11C-NPA Kinetic Analysis*

    RegionModelVT (mL/g)SE (%CV)Goodness of fit AIC
    Cerebellum1TCM3.4 ± 0.53.3 ± 1.2−29 ± 29
    2TCM3.3 ± 0.5†13.6 ± 8.0†−31 ± 32
    Striatum1TCM7.5 ± 1.51.9 ± 0.8−25 ± 38
    2TCM7.3 ± 1.4†4.5 ± 2.4†−24 ± 37

    • ↵* Values are mean ± SD; n = 8.

    • ↵† Significantly different from 1TCM (paired t test; P < 0.05).

  • TABLE 3

    Fractional Rate Constants and Total Distribution Volumes of 11C-NPA in Baboons*

    BaboonCerebellumStriatum
    Kinetic analysisGraphical analysis with arterial inputKinetic analysisGraphical analysis with arterial input
    K1 (mL/g/min)k2 (min)VT (mL/g)(VT [mL/g])K1 (mL/g/min)k2 (min)VT (mL/g)(VT [mL/g])
    A1.06 ± 0.210.29 ± 0.053.72 ± 0.533.39 ± 0.451.11 ± 0.280.13 ± 0.038.50 ± 1.518.02 ± 1.40
    B0.76 ± 0.11†0.24 ± 0.043.17 ± 0.312.90 ± 0.260.67 ± 0.13†0.10 ± 0.026.47 ± 0.97†6.07 ± 0.71†
    Mean0.91 ± 0.210.27 ± 0.033.44 ± 0.393.15 ± 0.35‡0.89 ± 0.310.12 ± 0.027.48 ± 1.447.05 ± 1.38‡

    • ↵* Values are mean ± SD; n = 4 per animal.

    • ↵† Significantly different from baboon A (unpaired t test; P < 0.05).

    • ↵‡ Significantly different from values derived with kinetic analysis (paired t test; P < 0.01).

  • TABLE 4

    Binding Parameters of 11C-NPA in Baboons*

    BaboonBP (mL/g)V3″ (unitless)
    Kinetic analysisGraphical with arterial inputKinetic analysisGraphical with arterial inputGraphical with reference region inputSRTM analysis
    A4.78 ± 1.024.63 ± 0.981.29 ± 0.171.36 ± 0.171.35 ± 0.171.41 ± 0.18
    B3.30 ± 0.67†3.17 ± 0.50†1.03 ± 0.12†1.09 ± 0.11†1.08 ± 0.11†1.13 ± 0.13†
    Mean4.04 ± 1.053.90 ± 1.03‡1.16 ± 0.181.23 ± 0.19‡1.22 ± 0.17‡1.27 ± 0.19§

    • ↵* Values are mean ± SD; n = 4 per animal.

    • ↵† Significantly different between the 2 baboons (unpaired t test; P < 0.05).

    • ↵‡ Significantly different from values derived with kinetic analysis (paired t test; P < 0.05).

    • ↵§ Significantly different from values derived with kinetic analysis (paired t test; P < 0.001).

  • TABLE 5

    Comparison of Outcome Measures Derived with Kinetic, Graphical, and SRTM Analysis

    ComparisonOutcomeDifferenceRegression equation y = mx + cr2
    Graphical with arterial input versus kineticVT CER−9.4% ± 4.7%†0.80x + 0.360.93
    VT STR−6.2% ± 3.7%†0.91x + 0.200.97
    BP−3.5% ± 4.2%*0.95x + 0.040.97
    V3″−5.3% ± 4.0%*0.98x + 0.080.89
    Graphical with reference region input versus kineticV3″−4.5% ± 3.7%*0.99x + 0.050.91
    SRTM versus kineticV3″−8.5% ± 2.5%†1.04x + 0.050.95

    • ↵* Significantly different from values derived with kinetic analysis (paired t test; P < 0.05; n = 8).

    • ↵† Significantly different from values derived with kinetic analysis (paired t test; P < 0.001; n = 8).

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