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OtherBasic Science Investigations

Evaluation of Pharmacokinetics of 4-Borono-2-18F-Fluoro-l-Phenylalanine for Boron Neutron Capture Therapy in a Glioma-Bearing Rat Model with Hyperosmolar Blood–Brain Barrier Disruption

Chia-Hung Hsieh, Yu-Fang Chen, Fu-Du Chen, Jeng-Jong Hwang, Jyh-Cheng Chen, Ren-Shen Liu, Ji-Jung Kai, Chi-Wei Chang and Hsin-Ell Wang
Journal of Nuclear Medicine November 2005, 46 (11) 1858-1865;
Chia-Hung Hsieh
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Yu-Fang Chen
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Fu-Du Chen
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Jeng-Jong Hwang
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Jyh-Cheng Chen
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Ren-Shen Liu
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Ji-Jung Kai
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Chi-Wei Chang
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Hsin-Ell Wang
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  • FIGURE 1.
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    FIGURE 1.

    Pharmacokinetics of 18F-FBPA for F98 glioma-bearing rats determined by PET. (A) Time–activity curves of 18F-FBPA in tumors and ipsilateral brains of F98 glioma-bearing rats derived from dynamic PET images after intracarotid (i.c.) injection with and without BBB-D and after intravenous (i.v.) injection. (B) Tumor-to-ipsilateral brain ratio of 18F-FBPA.

  • FIGURE 2.
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    FIGURE 2.

    Time–activity curves of 18F-FBPA in blood of F98 glioma-bearing Fischer 344 rats after intracarotid (i.c.) injection with and without BBB-D. Data points were fitted with open 2-compartment model (Cp = Ae−αt + Be−βt). r2 = 0.97–0.99.

  • FIGURE 3.
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    FIGURE 3.

    Biodistribution of 10B-BPA for F98 glioma-bearing rats. (A) Boron concentration in tumor, ipsilateral brain, contralateral brain, and blood of F98 glioma-bearing Fischer 344 rats after intracarotid injection of BPA (300 mg/kg) with BBB-D. (B) Tumor-to-normal tissue ratio of boron concentration. Rats were under ketamine mixture anesthesia.

  • FIGURE 4.
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    FIGURE 4.

    Boron concentration in tumor, ipsilateral brain (IB), contralateral brain (CB), and blood at 2.5 h after administration of 500 mg/kg of BW of BPA under isoflurane/ketamine mixture anesthesia.

  • FIGURE 5.
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    FIGURE 5.

    Correlation among tumor region of interest (ROI), k12/k21, and tumor-to-ipsilateral brain ratio. (A) Correlation between radioactivity of tumor ROI and k12/k21. (B) Correlation between tumor-to-ipsilateral brain ratio and k12/k21. Each point represents one rat. Radioactivity of tumor ROI and tumor-to-ipsilateral brain ratio were derived from PET images at 2.5 h after intracarotid injection of 18F-FBPA with and without BBB-D. k12/k21 ratio was obtained from pharmacokinetic analysis of blood of the same rat.

Tables

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    TABLE 1

    Estimated Pharmacokinetic Parameters Derived from Time–Activity Curves of Blood of F98 Glioma-Bearing Fischer 344 Rats After Intracarotid (i.c.) Injection of 18F-FBPA With and Without BBB-D

    Parameteri.c.i.c. + BBB-D
    kel (min−1)0.0071 ± 0.00140.0206 ± 0.0018
    k12 (min−1)0.0160 ± 0.00170.0260 ± 0.0016
    k21 (min−1)0.0061 ± 0.00040.0039 ± 0.0003
    V1 (mL)3.6 ± 0.13.1 ± 0.1
    k12/k212.6 ± 0.26.7 ± 0.5
    • Each point represents mean ± SD of 6 rats.

    • All P values for comparison of kel, k12, k21, V1, and k12/k21 were <0.01.

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    TABLE 2

    Biodistribution of 18F-FBPA in Tumor (T), Ipsilateral Brain (IB), Contralateral Brain (CB), and Blood (Bd) of F98 Glioma-Bearing Fischer 344 Rats at 0.5, 2.5, and 4.0 Hours after Intracarotid Administration of 18F-FBPA (29.6 MBq/kg of BW) with BBB-D

    Time (h)Accumulation (%ID/g)Ratio
    TIBCBBdT/IBT/CBT/Bd
    0.53.32 ± 0.921.15 ± 0.440.87 ± 0.201.72 ± 0.152.93.81.9
    2.52.63 ± 0.720.55 ± 0.210.46 ± 0.120.39 ± 0.084.85.76.7
    4.01.48 ± 0.250.42 ± 0.080.24 ± 0.040.18 ± 0.063.55.97.9
    • Each point represents mean ± SD of 4 or 5 rats. Rats were under isoflurane anesthesia.

    • View popup
    TABLE 3

    Boron Concentration in Tumor (Tumor [T] Implanted in Left Brain Region), Ipsilateral Brain (IB), Contralateral Brain (CB), and Blood (Bd) of F98 Glioma-Bearing Fischer 344 Rats at 2.5 Hours After Administration of BPA (500 mg/kg) by Various Routes

    RouteBoron concentration (μg/g)Ratio
    TIBCBBdT/IBT/CBT/Bd
    i.c. + BBB-D76.6 ± 12.112.1 ± 3.510.1 ± 1.59.2 ± 2.46.37.68.3
    i.c.43.1 ± 5.610.5 ± 0.99.3 ± 0.29.5 ± 1.44.14.64.5
    i.v.19.5 ± 4.57.8 ± 1.48.4 ± 1.69.0 ± 1.22.52.32.2
    • i.c. = intracarotid; i.v. = intravenous.

    • Each point represents mean ± SD of 5 or 6 rats. Rats were under ketamine mixture anesthesia.

    • View popup
    TABLE 4

    Biodistribution of 18F-FBPA and BPA in Tumor (T), Ipsilateral Brain (IB), Contralateral Brain (CB), and Blood (Bd) of F98 Glioma-Bearing Fischer 344 Rats at 2.5 Hours After Intracarotid Injection of a Mixture of 18F-FBPA (29.6 MBq/kg) and BPA (300 mg/kg) with BBB-D

    ElementAccumulationRatio
    TIBCBBdT/IBT/CBT/Bd
    18F (%ID/g)4.63 ± 0.720.61 ± 0.080.56 ± 0.120.52 ± 0.087.68.38.9
    10B (μg/g)45.5 ± 3.46.3 ± 0.235.6 ± 0.125.5 ± 0.337.28.18.3
    • Each point represents mean ± SD of 3 rats. Rats were under ketamine mixture anesthesia.

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Journal of Nuclear Medicine: 46 (11)
Journal of Nuclear Medicine
Vol. 46, Issue 11
November 1, 2005
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Evaluation of Pharmacokinetics of 4-Borono-2-18F-Fluoro-l-Phenylalanine for Boron Neutron Capture Therapy in a Glioma-Bearing Rat Model with Hyperosmolar Blood–Brain Barrier Disruption
Chia-Hung Hsieh, Yu-Fang Chen, Fu-Du Chen, Jeng-Jong Hwang, Jyh-Cheng Chen, Ren-Shen Liu, Ji-Jung Kai, Chi-Wei Chang, Hsin-Ell Wang
Journal of Nuclear Medicine Nov 2005, 46 (11) 1858-1865;

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Evaluation of Pharmacokinetics of 4-Borono-2-18F-Fluoro-l-Phenylalanine for Boron Neutron Capture Therapy in a Glioma-Bearing Rat Model with Hyperosmolar Blood–Brain Barrier Disruption
Chia-Hung Hsieh, Yu-Fang Chen, Fu-Du Chen, Jeng-Jong Hwang, Jyh-Cheng Chen, Ren-Shen Liu, Ji-Jung Kai, Chi-Wei Chang, Hsin-Ell Wang
Journal of Nuclear Medicine Nov 2005, 46 (11) 1858-1865;
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