Research ArticleBasic Science Investigations

In Vivo Measurement of the Affinity and Density of Metabotropic Glutamate Receptor Subtype 1 in Rat Brain Using 18F-FITM in Small-Animal PET

Tomoteru Yamasaki, Masayui Fujinaga, Kazunori Kawamura, Joji Yui, Akiko Hatori, Tomoyuki Ohya, Lin Xie, Hidekatsu Wakizaka, Yuichiro Yoshida, Toshimitsu Fukumura and Ming-Rong Zhang
Journal of Nuclear Medicine October 2012, 53 (10) 1601-1607; DOI: https://doi.org/10.2967/jnumed.112.105908

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    Time–activity curves of 18F-FITM in plasma of baseline and blocked rats. Blocked rats were pretreated with unlabeled FITM (1 mg/kg). Plasma input function was corrected by injection time and metabolites of 18F-FITM. Mean ± SE (n = 4 in each group).

  • FIGURE 2.
    FIGURE 2.

    Identification of time point at which equilibrium occurs for mGluR1 with 18F-FITM in thalamus (A), hippocampus (B), striatum (C), and cingulate cortex (D). Measured values in baseline experiments were subtracted from measured values in blocked experiments. Difference was defined as specific binding and fitted to set of 3 exponentials. Each equilibrium time is indicated by black arrow. Points are expressed as mean ± SE (n = 4).

  • FIGURE 3.
    FIGURE 3.

    Correlational scatterplots between BPND values based on EA RBA and those based on Logan plot GA. Plots show average datum points, with SEs in x- and y-axes (n = 4). ○ = thalamus; □ = hippocampus; △ = striatum; ⋄ = cingulate cortex.

  • FIGURE 4.
    FIGURE 4.

    PET of 18F-FITM distribution in rat brains after intravenous injection of unlabeled FITM. Rats were pretreated with different doses of unlabeled FITM: baseline (A), 1 μg/kg (B), 5 μg/kg (C), 30 μg/kg (D), and 1 mg/kg (E) administered). Coronal PET images were generated by averaging dynamic data at 0–90 min after bolus injection of 18F-FITM. Volumes of interest were placed on hippocampus, thalamus, striatum, and cingulate cortex. Hi = hippocampus; Th = thalamus; St = striatum; Ci = cingulate cortex.

  • FIGURE 5.
    FIGURE 5.

    Scatchard analyses for determination of mGluR1 Bmax and Kd of 18F-FITM in thalamus (A), hippocampus (B), striatum (C), and cingulate cortex (D). Regression lines are indicated for each region. The plots were expressed by average datum points, with standard errors in x- and y-axis (n = 3). [B] = bound ligand concentration.

Tables

  • TABLE 1

    Results of Logan Plot GA in Brain Regions of Baseline and Blocked Rats

    RegionBaseline VTBlocked VTVS = VT − VND*BPND
    Cerebellum114.0 ± 14.42.7 ± 0.3111.5 ± 14.443.9 ± 5.7
    Thalamus59.1 ± 5.82.5 ± 0.456.5 ± 5.822.3 ± 2.3
    Hippocampus47.9 ± 4.52.4 ± 0.445.4 ± 4.517.9 ± 1.8
    Striatum49.9 ± 5.52.6 ± 0.547.3 ± 5.518.6 ± 2.2
    Cingulate cortex42.0 ± 4.32.4 ± 0.339.4 ± 4.315.5 ± 1.7
    Pons6.2 ± 0.52.7 ± 0.43.7 ± 0.51.5 ± 0.2

    • ↵* Value of VND based on Lassen plot GA was 2.54 mL·cm−3 as shown in Supplemental Figure 3.

    • Data are mean ± SE, n = 4.

  • TABLE 2

    In Vivo Measurements of Kd, Bmax, and BP by Scatchard Analyses in Rat Brain

    RegionKd (nM)Bmax (pmol/mL)R2*BP†
    Thalamus2.136.30.9117.3
    Hippocampus2.127.50.8713.1
    Striatum1.522.20.9614.8
    Cingulate cortex1.520.50.9513.7

    • ↵* Coefficient of determination.

    • ↵† BP = Bmax/Kd.

Additional Files

Back to top

In this issue

Print
Download PDF
Article Alerts
Email Article
Citation Tools
Bookmark this article

Jump to section

Keywords