Research ArticleNeurology

Evaluation of 11C-BU99008, a PET Ligand for the Imidazoline2 Binding Site in Human Brain

Robin J. Tyacke, Jim F.M. Myers, Ashwin Venkataraman, Inge Mick, Samuel Turton, Jan Passchier, Stephen M. Husbands, Eugenii A. Rabiner, Roger N. Gunn, Philip S. Murphy, Christine A. Parker and David J. Nutt
Journal of Nuclear Medicine October 2018, 59 (10) 1597-1602; DOI: https://doi.org/10.2967/jnumed.118.208009

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    (A and B) Mean fits (sigmoid model) for parent fraction (A) and plasma-to-blood ratio (B) for unblocked scans (●), idazoxan-blocked scans (▪), and isocarboxazid scans (▲). Vertical bars represent SD. (C) Calculated parent plasma input function (triexponential) for unblocked scans (solid line), idazoxan-blocked scans (dashed line), and isocarboxazid scans (dotted line).

  • FIGURE 2.
    FIGURE 2.

    Representative time–activity curves for 11C-BU99008 uptake into human brain at baseline (A) and after partial blockade by treatment with 80 mg of idazoxan (B) in striatum (●), thalamus (▪), and cerebellum (♦). Dashed line = 1-tissue-compartment model; solid line = 2-tissue-compartment model; dotted line = multilinear analysis model.

  • FIGURE 3.
    FIGURE 3.

    SUV images demonstrating heterogeneous brain uptake in all regions and dose-dependent blockade by idazoxan.

  • FIGURE 4.
    FIGURE 4.

    Bar chart showing VT of 11C-BU99008 and effect of increasing doses of the mixed I2BS/α2-adrenoceptor ligand idazoxan. From left to right, each set of bars is mean ± SD for baseline, for 20-mg dose, for 40-mg dose, for 60-mg dose, and for 80-mg dose. Bars represent mean ± SD. Data are from a selection of representative brain regions.

  • FIGURE 5.
    FIGURE 5.

    Occupancy plots for subjects in heterologous block study, along with dose–response curve for individuals in whom occupancy was observed (inset). Median effective dose was 27.7 mg or 0.27 mg⋅kg−1, and estimated nondisplaceable distribution volume was 19.2 mL⋅cm−3.

Tables

  • TABLE 1

    Outcome Measures for Selected ROIs Using the 3 Models

    VT ± SD* (mL·cm−3)AIC*Test–retest variability†
    ROI1TCM2TCMMA1TCM2TCM1TCM2TCMMA
    Whole brain44.5 ± 6.148.8 ± 7.944.8 ± 6.1−237−32812.96.413.4
    Cerebellum39.3 ± 6.241.9 ± 6.939.6 ± 6.2−237−31014.610.814.9
    Brain stem62.7 ± 9.166.4 ± 10.163.2 ± 9.2−252−27613.711.714.6
    Occipital lobe38.6 ± 6.542.7 ± 8.638.8 ± 6.5−234−32312.88.113.3
    Insula63.3 ± 9.067.7 ± 11.863.9 ± 9.1−224−26714.611.014.8
    Frontal lobe41.6 ± 5.945.7 ± 7.942.0 ± 5.9−225−31612.64.713.1
    Cingulate58.3 ± 8.662.2 ± 9.758.8 ± 8.6−222−29314.610.215.1
    Parietal lobe39.2 ± 5.843.6 ± 8.739.5 ± 5.9−233−31812.45.612.8
    Amygdala89.8 ± 15.294.6 ± 20.391.1 ± 15.1−233−24223.224.723.3
    Hippocampus68.4 ± 11.477.7 ± 24.269.1 ± 11.5−225−26416.115.916.4
    Striatum102.7 ± 17.8105.7 ± 21.0104.2 ± 17.6−246−25916.916.717.4
    Thalamus75.3 ± 11.080.0 ± 14.176.0 ± 11.1−228−26414.69.515.2

    • ↵* n = 14.

    • ↵† n = 5.

    • AIC = Akaike Information Criterion; 1TCM = 1-tissue-compartment model; 2TCM = 2-tissue-compartment model; MA = multilinear analysis model.

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