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OtherBasic Science Investigations

Preclinical Evaluation of the Penciclovir Analog 9-(4-[18F]Fluoro-3-Hydroxymethylbutyl)Guanine for In Vivo Measurement of Suicide Gene Expression with PET

Mian M. Alauddin, Antranik Shahinian, Erlinda M. Gordon, James R. Bading and Peter S. Conti
Journal of Nuclear Medicine November 2001, 42 (11) 1682-1690;
Mian M. Alauddin
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Antranik Shahinian
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Erlinda M. Gordon
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James R. Bading
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Peter S. Conti
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  • FIGURE 1.
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    FIGURE 1.

    In vitro incorporation of [18F]FHBG into transduced (+) and nontransduced (−) cells at 1 and 5 h. Data are average of 3 experiments ± SEM; P < 0.001 for both time points (Student t test). cpm = counts per minute.

  • FIGURE 2.
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    FIGURE 2.

    HPLC radiochromatograms of [18F]FHBG (a) and its metabolites (b–d) in HT-29 tumor cells after 5-h incubation. (A) Transduced cells. (B) Nontransduced cells.

  • FIGURE 3.
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    FIGURE 3.

    Blood clearance curve of 18F activity in nude mice bearing transduced tumors after intravenous injection of [18F]FHBG (semilogarithmic plot; n = 3).

  • FIGURE 4.
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    FIGURE 4.

    Time–activity curve for arterial plasma from cynomolgus monkeys after intravenous injection of [18F]FHBG (semilogarithmic plot). Total plasma volume was estimated to be 2.5% of body weight in calculating %ID in plasma. Data are mean ± SEM from 2 monkeys. Error bars are smaller than symbols for most data points. Solid line is intended to guide the eye and does not represent model fit to data.

  • FIGURE 5.
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    FIGURE 5.

    HPLC radiochromatogram of [18F]FHBG and its metabolites in plasma taken 60 min after injection from cynomolgus monkey. For study shown, 86% of recovered activity was on [18F]FHBG as calculated by FHBG peak area ÷ total area under radiochromatogram.

  • FIGURE 6.
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    FIGURE 6.

    Distribution of 18F from [18F]FHBG in cynomolgus monkey. Images are coronal (left) and sagittal (right) 2-dimensional projections from multicouch-position scan obtained 104–140 min after intravenous injection of [18F]FHBG. Note that skeleton is not visualized, indicating that 18F uptake in bone and marrow was relatively low.

  • FIGURE 7.
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    FIGURE 7.

    Biodistribution of radiolabel from [18F]FHBG and [18F]FHPG in nude mice bearing transduced tumors. (A) Uptake at 2 h after injection. (B) Uptake at 5 h after injection. (C) Tumor-to-normal ratios at 2 h after injection. (D) Tumor-to-normal ratios at 5 h after injection. Data are mean ± SEM (n = 5). *P < 0.05 for difference between FHPG and FHBG.

Tables

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    TABLE 1

    Biodistribution of [18F]FHBG in Tumor-Bearing Mice at 2 Hours

    TissueNontransduced tumor modelTransduced tumor model
    %ID/gTumor-to-tissue ratio%ID/gTumor-to-tissue ratio
    Blood0.035 ± 0.0033.37 ± 0.110.041 ± 0.00212.12 ± 0.91
    Skin0.056 ± 0.0042.09 ± 0.120.046 ± 0.00417.12 ± 4.25
    Muscle0.034 ± 0.0023.49 ± 0.220.039 ± 0.00521.93 ± 4.09
    Bone0.243 ± 0.0130.53 ± 0.060.258 ± 0.0242.46 ± 0.33
    Heart0.037 ± 0.0033.24 ± 0.180.033 ± 0.00524.93 ± 3.75
    Lung0.055 ± 0.0052.14 ± 0.080.052 ± 0.00412.59 ± 2.29
    Liver0.007 ± 0.0141.65 ± 0.320.119 ± 0.0166.29 ± 0.89
    Spleen0.074 ± 0.0061.62 ± 0.110.068 ± 0.00610.35 ± 2.08
    Pancreas0.073 ± 0.0061.79 ± 0.180.074 ± 0.0067.96 ± 1.14
    Stomach0.062 ± 0.0092.45 ± 0.270.075 ± 0.0308.27 ± 1.23
    Intestine0.099 ± 0.0081.47 ± 0.230.110 ± 0.0054.74 ± 0.43
    Kidney0.129 ± 0.0070.98 ± 0.120.116 ± 0.0125.48 ± 0.67
    Tumor0.113 ± 0.0080.508 ± 0.049*
    • ↵* P < 0.05 compared with nontransduced tumor (Student t test on paired samples).

    • Data are mean ± SEM of 5 animals.

    • View popup
    TABLE 2

    Biodistribution of [18F]FHBG in Tumor-Bearing Mice at 5 Hours

    TissueNontransduced tumor modelTransduced tumor model
    %ID/gTumor-to-tissue ratio%ID/gTumor-to-tissue ratio
    Blood0.017 ± 0.0011.58 ± 0.140.017 ± 0.00120.71 ± 1.06
    Skin0.026 ± 0.0011.05 ± 0.070.030 ± 0.00111.52 ± 0.62
    Muscle0.017 ± 0.0011.64 ± 0.120.022 ± 0.00322.23 ± 2.41
    Bone0.225 ± 0.0150.13 ± 0.010.220 ± 0.0151.71 ± 0.15
    Heart0.020 ± 0.0011.48 ± 0.150.023 ± 0.00115.74 ± 0.99
    Lung0.031 ± 0.0020.89 ± 0.060.022 ± 0.00115.73 ± 0.93
    Liver0.047 ± 0.0020.54 ± 0.020.034 ± 0.00211.23 ± 1.01
    Spleen0.050 ± 0.0030.55 ± 0.040.043 ± 0.0039.08 ± 0.99
    Pancreas0.028 ± 0.0031.46 ± 0.280.029 ± 0.00111.49 ± 0.51
    Stomach0.050 ± 0.0030.84 ± 0.080.030 ± 0.00111.51 ± 0.68
    Intestine0.064 ± 0.0050.47 ± 0.050.058 ± 0.0025.87 ± 0.27
    Kidney0.054 ± 0.0020.49 ± 0.030.048 ± 0.0058.86 ± 1.11
    Tumor0.025 ± 0.0100.335 ± 0.070*
    • ↵* P < 0.001 compared with nontransduced tumor (Student t test on paired samples).

    • Data are mean ± SEM of 5 animals.

    • View popup
    TABLE 3

    Distribution of Radiolabel from [18F]FHBG Among Acid-Soluble Molecules in Plasma and Urine of Cynomolgus Monkeys

    TissueTime after injection (min)Recovered activity on FHBG*† (%)
    Plasma099.5 ± 0.2 (2)
    Plasma1591 ± 1 (2)
    Plasma6087 ± 1 (2)
    Plasma12069 ± 6 (2)
    Urine12097 (1)
    • ↵* Data are mean ± SEM (no. of observations).

    • ↵† Measured recovery of radioactivity from HPLC was 89% ± 2% (mean ± SEM), which was determined according to method described in legend to Figure 5.

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Journal of Nuclear Medicine
Vol. 42, Issue 11
November 1, 2001
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Preclinical Evaluation of the Penciclovir Analog 9-(4-[18F]Fluoro-3-Hydroxymethylbutyl)Guanine for In Vivo Measurement of Suicide Gene Expression with PET
Mian M. Alauddin, Antranik Shahinian, Erlinda M. Gordon, James R. Bading, Peter S. Conti
Journal of Nuclear Medicine Nov 2001, 42 (11) 1682-1690;

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Preclinical Evaluation of the Penciclovir Analog 9-(4-[18F]Fluoro-3-Hydroxymethylbutyl)Guanine for In Vivo Measurement of Suicide Gene Expression with PET
Mian M. Alauddin, Antranik Shahinian, Erlinda M. Gordon, James R. Bading, Peter S. Conti
Journal of Nuclear Medicine Nov 2001, 42 (11) 1682-1690;
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