Research ArticleClinical Investigations

Test–Retest Reproducibility of Binding Parameters in Humans with 11C-LY2795050, an Antagonist PET Radiotracer for the κ Opioid Receptor

Mika Naganawa, Ming-Qiang Zheng, Shannan Henry, Nabeel Nabulsi, Shu-Fei Lin, Jim Ropchan, David Labaree, Soheila Najafzadeh, Michael Kapinos, Johannes Tauscher, Alexander Neumeister, Richard E. Carson and Yiyun Huang
Journal of Nuclear Medicine February 2015, 56 (2) 243-248; DOI: https://doi.org/10.2967/jnumed.114.147975

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    Mean ± SD of total plasma activity (A), parent fraction in plasma (B), and metabolite-corrected plasma activity (C) over time after injection of 11C-LY2795050 in test (closed circles, n = 16) and retest (open circles, n = 16) scans. A and C are displayed in SUV units (concentration/[injected dose/body weight]).

  • FIGURE 2.
    FIGURE 2.

    MR images and coregistered PET images summed from 30 to 90 min after injection of 11C-LY2795050: MR images (A), test scan (B), and retest scan (C). PET images are displayed in SUV units. SUV images were averaged across all subjects.

  • FIGURE 3.
    FIGURE 3.

    Time–activity curves from 1 subject for 6 selected regions after injection of 11C-LY2795050 under test (A) and retest (B) conditions. Fits with MA1 (t* = 30 min) and 2TC models are displayed as solid and dotted lines, respectively.

Tables

  • TABLE 1

    Subject Information and PET Scan Parameters

    ParameterTest (n = 16)Retest (n = 16)
    Age (y)28 ± 728 ± 7
    Body weight (kg)78.6 ± 11.478.6 ± 11.4
    Injected dose (MBq)390 ± 135461 ± 178
    Specific activity (MBq/nmol)18.0 ± 6.421.8 ± 9.6
    Injected mass (μg)9.1 ± 1.29.1 ± 1.3

    • Data are mean ± SD.

  • TABLE 2

    Binding Parameters Derived from MA1 Method

    VT (mL/cm3)VT/fP (mL/cm3)BPNDBPP (mL/cm3)BPF (mL/cm3)
    RegionTestRetestTestRetestTestRetestTestRetestTestRetest
    Amygdala4.17 (13)3.98 (13)439 (18)448 (26)1.55 (19)1.45 (21)2.52 (15)2.33 (17)265 (21)264 (30)
    Insula3.40 (11)3.38 (10)357 (15)379 (22)1.07 (17)1.08 (14)1.74 (11)1.74 (8)183 (15)195 (20)
    Ant. cingulate cortex3.28 (12)3.26 (11)345 (16)365 (23)1.00 (14)1.00 (15)1.63 (12)1.61 (11)171 (17)181 (22)
    Globus pallidus3.13 (11)3.11 (13)329 (16)349 (26)0.92 (23)0.91 (21)1.47 (16)1.46 (20)156 (21)164 (30)
    Putamen2.90 (11)2.91 (10)305 (16)326 (22)0.77 (20)0.79 (21)1.25 (14)1.27 (15)132 (19)142 (24)
    Temporal cortex2.65 (11)2.64 (10)278 (15)295 (21)0.62 (24)0.62 (22)0.99 (17)0.99 (14)104 (20)111 (20)
    Frontal cortex2.64 (11)2.63 (11)278 (16)294 (22)0.61 (22)0.61 (20)0.98 (16)0.98 (14)104 (21)110 (22)
    Occipital cortex2.47 (11)2.45 (10)259 (15)274 (21)0.51 (30)0.51 (27)0.81 (22)0.81 (19)85 (24)90 (23)
    Hippocampus2.35 (11)2.30 (11)247 (15)259 (25)0.44 (30)0.42 (34)0.70 (25)0.66 (30)73 (26)75 (38)
    Caudate2.28 (11)2.28 (12)240 (16)256 (26)0.40 (45)0.40 (47)0.62 (40)0.63 (42)66 (43)72 (51)
    Post. cingulate cortex2.19 (12)2.17 (13)230 (17)244 (24)0.33 (43)0.34 (47)0.53 (36)0.53 (43)56 (38)59 (46)
    Thalamus2.19 (9)2.17 (9)230 (15)244 (23)0.34 (43)0.34 (47)0.53 (37)0.53 (43)57 (39)60 (45)
    Centrum semiovale2.19 (11)2.14 (16)230 (15)241 (27)0.34 (46)0.31 (48)0.54 (38)0.50 (43)56 (40)56 (47)
    Cerebellum1.94 (16)1.92 (16)203 (19)216 (26)0.17 (0)0.17 (0)0.28 (16)0.28 (16)30 (19)31 (26)

    • Ant. = anterior; Post. = posterior.

    • Data are mean of 16 subjects, with each value measured twice in test and retest scans. Data in parentheses are percentage coefficient of variation (intersubject variability).

  • TABLE 3

    Test–Retest Reproducibility of Volume of Distribution

    2TC, VT (mL/cm3)MA1, VT (mL/cm3)MA1, VT/fP (mL/cm3)
    RegionaTRVTRVICCaTRVTRVICCaTRVTRVICC
    Amygdala9%3% ± 11%0.39 (-0.18;0.77)12%5% ± 14%0.41 (-0.08;0.74)18%−1% ± 22%0.55 (0.11;0.82)
    Insula7%−1% ± 9%0.58 (0.13;0.84)7%0% ± 9%0.68 (0.31;0.87)14%−5% ± 18%0.46 (-0.02;0.77)
    Ant. cingulate cortex8%0% ± 10%0.61 (0.19;0.84)6%0% ± 8%0.78 (0.50;0.92)14%−5% ± 16%0.60 (0.17;0.84)
    Globus pallidus8%0% ± 10%0.70 (0.32;0.89)8%1% ± 9%0.74 (0.41;0.90)15%−4% ± 18%0.55 (0.11;0.82)
    Putamen7%−2% ± 8%0.73 (0.37;0.90)6%0% ± 7%0.81 (0.55;0.93)13%−6% ± 16%0.57 (0.14;0.83)
    Temporal cortex9%0% ± 11%0.50 (0.04;0.79)7%0% ± 8%0.70 (0.33;0.88)13%−5% ± 17%0.50 (0.04;0.79)
    Frontal cortex8%0% ± 10%0.61 (0.20;0.84)7%0% ± 8%0.74 (0.41;0.90)13%−5% ± 17%0.54 (0.09;0.81)
    Occipital cortex9%0% ± 11%0.52 (0.06;0.80)6%1% ± 7%0.77 (0.46;0.91)13%−5% ± 16%0.52 (0.07;0.80)
    Hippocampus9%2% ± 10%0.63 (0.22;0.85)8%2% ± 9%0.67 (0.28;0.87)15%−4% ± 18%0.54 (0.10;0.81)
    Caudate7%−2% ± 8%0.77 (0.42;0.92)6%0% ± 7%0.82 (0.56;0.93)13%−5% ± 16%0.60 (0.18;0.84)
    Post. cingulate cortex9%1% ± 11%0.72 (0.37;0.89)7%1% ± 9%0.76 (0.45;0.91)14%−5% ± 17%0.61 (0.19;0.84)
    Thalamus8%0% ± 9%0.50 (0.04;0.79)7%1% ± 9%0.54 (0.09;0.81)15%−5% ± 18%0.51 (0.05;0.79)
    Centrum semiovale10%4% ± 13%0.57 (0.12;0.83)10%3% ± 13%0.57 (0.14;0.83)18%−3% ± 20%0.52 (0.06;0.80)
    Cerebellum7%0% ± 9%0.85 (0.63;0.94)6%1% ± 8%0.89 (0.71;0.96)13%−5% ± 17%0.64 (0.23;0.85)

    • Ant. = anterior; Post. = posterior.

    • 2TC VT estimates with relative SE > 10% or k4 < 0.001 min−1 were excluded from calculation. Data within parentheses are 95% confidence intervals.

  • TABLE 4

    Test–Retest Reproducibility of Binding Potential

    BPNDBPP (mL/cm3)BPF (mL/cm3)
    RegionaTRVTRVICCaTRVTRVICCaTRVTRVICC
    Amygdala13%7% ± 17%0.56 (0.12;0.82)16%8% ± 20%0.24 (−0.26;0.65)22%2% ± 27%0.53 (0.07;0.80)
    Insula7%−1% ± 8%0.88 (0.71;0.96)10%0% ± 11%0.36 (−0.14;0.71)15%−6% ± 19%0.33 (−0.17;0.70)
    Ant. cingulate cortex5%0% ± 7%0.91 (0.76;0.97)8%1% ± 9%0.67 (0.29;0.87)14%−5% ± 16%0.61 (0.20;0.84)
    Globus pallidus9%1% ± 11%0.89 (0.71;0.96)10%1% ± 13%0.76 (0.45;0.91)18%−4% ± 20%0.62 (0.20;0.85)
    Putamen7%−2% ± 8%0.93 (0.82;0.98)7%−2% ± 8%0.85 (0.62;0.94)14%−7% ± 15%0.66 (0.27;0.87)
    Temporal cortex6%−1% ± 8%0.95 (0.87;0.98)9%−1% ± 10%0.77 (0.47;0.91)15%−6% ± 18%0.59 (0.16;0.83)
    Frontal cortex5%−1% ± 7%0.94 (0.83;0.98)8%0% ± 10%0.76 (0.45;0.91)15%−6% ± 18%0.63 (0.22;0.85)
    Occipital cortex9%−1% ± 13%0.95 (0.87;0.98)10%0% ± 12%0.86 (0.66;0.95)14%−6% ± 18%0.71 (0.36;0.89)
    Hippocampus15%7% ± 17%0.89 (0.72;0.96)17%7% ± 18%0.79 (0.51;0.92)22%2% ± 25%0.70 (0.33;0.88)
    Caudate10%−2% ± 16%0.98 (0.95;0.99)10%−1% ± 14%0.96 (0.90;0.99)15%−7% ± 17%0.88 (0.69;0.95)
    Post. cingulate cortex22%9% ± 44%0.92 (0.80;0.97)24%10% ± 44%0.86 (0.66;0.95)27%5% ± 45%0.82 (0.57;0.93)
    Thalamus31%22% ± 81%0.96 (0.90;0.99)36%24% ± 86%0.91 (0.77;0.97)45%22% ± 98%0.83 (0.59;0.94)
    Centrum semiovale33%16% ± 59%0.82 (0.58;0.93)35%15% ± 60%0.70 (0.34;0.88)42%11% ± 64%0.67 (0.29;0.87)

    • Ant. = anterior; Post. = posterior.

    • Data within parentheses are 95% confidence intervals.

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