Research ArticleBasic Science Investigations

Quantitative Preclinical Imaging of TSPO Expression in Glioma Using N,N-Diethyl-2-(2-(4-(2-18F-Fluoroethoxy)Phenyl)-5,7-Dimethylpyrazolo[1,5-a]Pyrimidin-3-yl)Acetamide

Dewei Tang, Matthew R. Hight, Eliot T. McKinley, Allie Fu, Jason R. Buck, R. Adam Smith, Mohammed Noor Tantawy, Todd E. Peterson, Daniel C. Colvin, M. Sib Ansari, Michael Nickels and H. Charles Manning
Journal of Nuclear Medicine February 2012, 53 (2) 287-294; DOI: https://doi.org/10.2967/jnumed.111.095653

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    Chemical structure of DPA-714 (inset). Radioligand displacement of 3H-PK 11195 using DPA-714 in C6 glioma cell lysate (inhibitory concentration of 50%, 10.9 nM). conc = concentration.

  • FIGURE 2.
    FIGURE 2.

    (A) T2-weighted MR image of C6 glioma–bearing rat in right brain hemisphere. (B) Coronal PET image obtained from dynamic scan of 18F-DPA-714 PET (summed dynamic scan, 0–90 min). (C) 18F-DPA-714 time–activity curves for tumor (blue), contralateral brain (green), and plasma (red). (D) Transverse PET image obtained from dynamic scan of 18F-DPA-714 PET (summed dynamic scan, 0–90 min). (E) Standard hematoxylin and eosin staining of serial tissue section. (F) Immunohistochemistry analysis of TSPO expression in typical C6 glioma. Tumor location is indicated with arrows in images. %ID/cc = percentage injected dose per cubic centimeter.

  • FIGURE 3.
    FIGURE 3.

    In vivo displacement of 18F-DPA-714 in C6 glioma–bearing rat. Relative 18F-DPA-714 uptake before (A) and after (B) intravenous infusion of excess of DPA-714. (C) 18F-DPA-714 time–activity curves generated for tumor (blue), contralateral brain (green), and plasma (red). %ID/cc = percentage injected dose per cubic centimeter.

  • FIGURE 4.
    FIGURE 4.

    Comparison of 18F-PBR06 and 18F-DPA-714 in same glioma-bearing rat. (A) T2-weighted MR image of rat bearing C6 glioma in right hemisphere. (B) 18F-DPA-714 PET image (summed dynamic scan over last 30 min). (C) 18F-PBR06 PET image (summed dynamic scan over last 30 min). (D) 18F-DPA-714 time–activity curves generated for tumor (blue), contralateral brain (green), and plasma (red). For comparison, 18F-PBR06 time–activity curves are shown in black. %ID/cc = percentage injected dose per cubic centimeter.

  • FIGURE 5.
    FIGURE 5.

    Pharmacokinetic model fit of typical 18F-DPA-714 time–activity curves to 3-compartment, 4-kinetic-parameter (A) and 2-compartment, 2-kinetic-parameter (B) models. Time–activity curves for tumor (blue), contralateral brain (green), and plasma (red) are shown with associated model fit. %ID/cc = percentage injected dose per cubic centimeter.

  • FIGURE 6.
    FIGURE 6.

    Representative graphical analysis of VT for a subject from this investigation. Fit was performed for normal brain (A) and for tumor (B). Solid gray line = linear regression (start time for linear regression, “t*”).

Tables

  • TABLE 1

    HPLC Radiometabolite Analysis of 18F-DPA-714

    Time after injection (min)Percentage 18F-DPA-714Percentage 18F-fluoridePercentage metabolite
    2 (n = 7)95 ± 6.02 ± 3.33 ± 3.7
    12 (n = 7)68 ± 7.413 ± 6.719 ± 5.8
    30 (n = 7)44 ± 8.937 ± 5.419 ± 8.8
    60 (n = 7)27 ± 6.250 ± 15.023 ± 7.3
    90 (n = 5)22 ± 17.864 ± 12.114 ± 3.8

    • Data are mean ± SD.

  • TABLE 2

    Parameter Estimations for 18F-DPA-714 Uptake

    Tissue typeK1/k2 (mL/g)k3/k4VT (mL/g)*VT (mL/g)†VT (mL/g)†%ID/cc
    Tumor (n = 11)6.867 ± 1.2268.913 ± 1.15570.033 ± 14.72957.44 ± 11.7420.331 ± 0.036
    Brain (n = 11)3.619 ± 0.5514.024 ± 0.84215.963 ± 3.56614.57 ± 2.8230.088 ± 0.011
    P0.07620.00210.00170.0029<0.0001

    • ↵* From kinetic parameters.

    • ↵† From graphical analysis.

    • Data are mean ± SEM.

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