OtherBASIC SCIENCE INVESTIGATIONS

11C-AC-5216: A Novel PET Ligand for Peripheral Benzodiazepine Receptors in the Primate Brain

Ming-Rong Zhang, Katsushi Kumata, Jun Maeda, Kazuhiko Yanamoto, Akiko Hatori, Maki Okada, Makoto Higuchi, Shigeru Obayashi, Tetsuya Suhara and Kazutoshi Suzuki
Journal of Nuclear Medicine November 2007, 48 (11) 1853-1861; DOI: https://doi.org/10.2967/jnumed.107.043505

Article Figures & Data

Figures

  • FIGURE 1. 
    FIGURE 1. 

    Synthesis scheme for AC-5216, desmethyl precursor (compound 1), and 11C-AC-5216. Reaction conditions included the following: a—BOP, DMF, room temperature, Et3N, 3 h; b—EtoH, reflux, 30 min; c—DMF, 100°C, 6 h; d—NaH, DMF, room temperature, 3 h; e—11C-CH3I, DMF, 30°C, 3 min.

  • FIGURE 2. 
    FIGURE 2. 

    Effect of nonradioactive AC-5216 (1 mg/kg), PBR-selective PK11195 (1 mg/kg), and CBR-selective flumazenil (1 mg/kg) and Ro15-4513 (1 mg/kg) on 11C-AC-5216 radioactivity (mean ± SD, n = 5) in selected regions of mouse brains at 30 min after injection of 11C-AC-5216 (8 MBq).

  • FIGURE 3. 
    FIGURE 3. 

    (A) Time–activity curves for 11C-AC-5216 in occipital cortex, frontal cortex, cerebellum, striatum, and thalamus of monkey brain. Uptake was expressed as percentage injected dose per volume (%ID/mL). (B) Mean image of 11C-AC-5216 in brain of rhesus monkey. PET image was generated by averaging for whole scan and was overlaid on MR image.

  • FIGURE 4. 
    FIGURE 4. 

    (A) Effects of compounds with affinity for PBR on 11C-AC-5216 binding in occipital cortex of monkey brain. (B) Radioactivity in occipital cortex was normalized to initial maximum uptake of ligand, which was designated as 100%.

  • FIGURE 5. 
    FIGURE 5. 

    Percentages (mean ± SD, n = 3) of unchanged 11C-AC-5216 in mouse plasma and brain homogenate at several time points after injection of 11C-AC-5216 (37 MBq).

  • FIGURE 6. 
    FIGURE 6. 

    Percentage of unchanged 11C-AC-5216 in monkey plasma at several time points after injection of 11C-AC-5216 (250 MBq).

Tables

  • TABLE 1

    Tissue Distribution in 5 Mice

    Distribution (mean ± SD % ID/g of tissue) at:
    Tissue1 min5 min15 min30 min60 min
    Blood1.79 ± 0.521.58 ± 1.050.41 ± 0.110.65 ± 0.570.33 ± 0.14
    Lung80.76 ± 9.6152.79 ± 8.6628.01 ± 5.7916.15 ± 1.9713.65 ± 2.28
    Heart11.30 ± 1.959.69 ± 1.638.36 ± 1.115.11 ± 1.053.52 ± 0.41
    Liver2.48 ± 0.513.88 ± 0.526.00 ± 0.286.44 ± 0.587.36 ± 1.46
    Spleen2.02 ± 0.696.83 ± 1.117.58 ± 1.227.25 ± 1.257.77 ± 1.21
    Adrenal gland2.23 ± 2.0211.27 ± 2.025.90 ± 3.707.06 ± 3.2011.89 ± 3.35
    Kidney9.39 ± 1.2511.05 ± 1.6213.65 ± 2.0711.86 ± 1.5212.78 ± 3.18
    Intestine6.37 ± 1.556.66 ± 0.326.57 ± 0.454.95 ± 0.736.87 ± 1.34
    Testicle0.13 ± 0.360.51 ± 0.030.51 ± 0.080.46 ± 0.100.60 ± 0.15
    Brain1.15 ± 0.340.80 ± 0.130.58 ± 0.080.35 ± 0.050.31 ± 0.02
  • TABLE 2

    Brain Regional Distribution in 5 Mice

    Distribution (mean ± SD % ID/g of tissue) at:
    Tissue1 min5 min15 min30 min60 min
    Cerebellum1.09 ± 0.431.38 ± 0.351.45 ± 0.291.02 ± 0.570.85 ± 0.26
    Olfactory bulb1.98 ± 0.582.03 ± 0.562.53 ± 0.481.85 ± 0.970.63 ± 0.39
    Hippocampus0.32 ± 0.050.58 ± 0.230.46 ± 0.130.32 ± 0.160.18 ± 0.21
    Striatum0.65 ± 0.120.69 ± 0.140.32 ± 0.280.42 ± 0.300.21 ± 0.36
    Cerebral cortex1.52 ± 0.251.02 ± 0.290.55 ± 0.140.56 ± 0.230.37 ± 0.19
    Thalamus0.84 ± 0.210.95 ± 0.190.25 ± 0.080.34 ± 0.150.41 ± 0.06
    Hypothalamus0.53 ± 0.150.65 ± 0.320.41 ± 0.250.35 ± 0.190.12 ± 0.10
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