Research ArticleClinical Investigations

Brain and Whole-Body Imaging of Nociceptin/Orphanin FQ Peptide Receptor in Humans Using the PET Ligand 11C-NOP-1A

Talakad G. Lohith, Sami S. Zoghbi, Cheryl L. Morse, Maria F. Araneta, Vanessa N. Barth, Nancy A. Goebl, Johannes T. Tauscher, Victor W. Pike, Robert B. Innis and Masahiro Fujita
Journal of Nuclear Medicine March 2012, 53 (3) 385-392; DOI: https://doi.org/10.2967/jnumed.111.097162

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    Parent radioligand fraction, radioactivity concentrations (conc), and radiometabolite profile in plasma from 40-y-old healthy man injected with 755 MBq of 11C-NOP-1A. (A) Fraction of unchanged parent radioligand 11C-NOP-1A (○) in plasma fitted by Hill function. (B) Time course of parent 11C-NOP-1A concentration (○) in arterial plasma fitted by multiplying triexponential-fitted total plasma radioactivity and Hill function–fitted plasma parent fraction. (C) Radiochromatogram illustrating plasma composition 40 min after injection of 11C-NOP-1A. Radioactivity was measured in counts per second (cps). Peaks A to D and parent are labeled with increasing lipophilicity.

  • FIGURE 2.
    FIGURE 2.

    MRI and MA1 parametric PET images of 44-y-old healthy man injected with 738 MBq of 11C-NOP-1A: MRI anatomic images (A) and MA1 parametric images (B) in axial (left), sagittal (middle), and coronal (right) views. Each pixel value represents VT and is indicated in VT color scale on right.

  • FIGURE 3.
    FIGURE 3.

    Representative brain uptake with compartmental fitting from 40-y-old healthy man injected with 755 MBq of 11C-NOP-1A. Concentration of radioactivity from 3 regions is shown: putamen (○), with highest uptake; cingulate cortex (•), with medium uptake; and cerebellum (□), with lowest uptake. Line represents unconstrained 2-tissue-compartment fitting.

  • FIGURE 4.
    FIGURE 4.

    Comparison of total VT in various brain regions. VT values were calculated in 7 subjects injected with 11C-NOP-1A using unconstrained 2-tissue-compartment model for VOI data and Logan and MA1 methods for voxel data (Loganvoxel and MA1voxel). (A) Mean VT values obtained by both MA1voxel (hatched bars) and Loganvoxel (white bars) were significantly lower than those obtained by 2-tissue-compartment model (black bars) (P < 0.05 by factorial repeated-measures ANOVA). Loganvoxel gave significantly smaller VT values than MA1voxel (P < 0.05). Data represent mean ± SD of all 7 subjects. (B) Scatterplot comparing mean VT values from each region (excluding cerebellum) by MA1voxel method vs. 2-tissue-compartment model in 40-y-old healthy man injected with 755 MBq of 11C-NOP-1A. Simple linear regression was significant (Pearson R2 = 0.95, P < 0.0001), with linear regression line equation y = 1.05x + 0.1. Solid line represents line of best fit. Dashed lines are 95% confidence intervals. FC = frontal cortex; PA = parietal cortex; OC = occipital cortex; TC = temporal cortex; MT = medial temporal cortex; CC = cingulate cortex; CA = caudate cortex; PU = putamen; TH = thalamus; CE = cerebellum.

  • FIGURE 5.
    FIGURE 5.

    Whole-body images of healthy 22-y-old man show distribution of radioactivity at about 6, 50, and 102 min after injection of 480 MBq of 11C-NOP-1A. In addition to high uptake in brain, image at 6 min shows high uptake in lungs and heart. Images at 50 and 102 min show excretion of radioactivity via liver, small bowel, and urinary bladder. These images were created by summing all coronal slices at each time point. Pixel values were decay-corrected to time of injection and displayed with same gray scale.

  • FIGURE 6.
    FIGURE 6.

    Time–activity curves for 10 source organs after 11C-NOP-1A injection. Data are corrected for radioactive decay and expressed as mean and SD (symbol and error bars) from 9 subjects.

Tables

  • TABLE 1

    Regional VT of 11C-NOP-1A in Human Brain Determined from Large VOIs or from Individual Voxels

    VT (mL cm−3)
    VOIVoxel
    Brain regionTwo-tissueLoganVOIMA1VOILoganvoxelMA1voxel
    Temporal cortex10.1 ± 1.69.6 ± 1.69.5 ± 1.58.9 ± 1.79.4 ± 1.8
    Cingulate cortex9.4 ± 1.58.9 ± 1.58.9 ± 1.58.3 ± 1.58.8 ± 1.6
    Putamen10.0 ± 1.89.5 ± 1.79.4 ± 1.78.9 ± 1.79.3 ± 1.8
    Thalamus9.0 ± 1.68.5 ± 1.58.5 ± 1.58.0 ± 1.68.5 ± 1.6
    Cerebellum5.6 ± 0.85.2 ± 0.85.3 ± 0.84.8 ± 1.05.1 ± 1.0

    • Values are mean ± SD from 7 humans using 120 min of brain and plasma data. Two-tissue-compartment model was fit with no constraints. Subscript “VOI” denotes that concentration of radioactivity from large VOIs (e.g., entire temporal cortex of 251 cm3) was analyzed. Subscript “voxel” denotes that concentration of radioactivity of individual voxel (8 mm3) was analyzed. Voxels of resulting parametric image have values equal to VT.

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