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Research ArticleBasic Science Investigations

Novel PET Probes 18F-BCPP-EF and 18F-BCPP-BF for Mitochondrial Complex I: A PET Study in Comparison with 18F-BMS-747158-02 in Rat Brain

Hideo Tsukada, Shingo Nishiyama, Dai Fukumoto, Masakatsu Kanazawa and Norihiro Harada
Journal of Nuclear Medicine March 2014, 55 (3) 473-480; DOI: https://doi.org/10.2967/jnumed.113.125328
Hideo Tsukada
Central Research Laboratory, Hamamatsu Photonics K.K., Hamamatsu, Shizuoka, Japan
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Shingo Nishiyama
Central Research Laboratory, Hamamatsu Photonics K.K., Hamamatsu, Shizuoka, Japan
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Dai Fukumoto
Central Research Laboratory, Hamamatsu Photonics K.K., Hamamatsu, Shizuoka, Japan
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Masakatsu Kanazawa
Central Research Laboratory, Hamamatsu Photonics K.K., Hamamatsu, Shizuoka, Japan
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Norihiro Harada
Central Research Laboratory, Hamamatsu Photonics K.K., Hamamatsu, Shizuoka, Japan
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  • FIGURE 1.
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    FIGURE 1.

    Distribution and kinetics of 18F-BCPP-EF (A), 18F-BCPP-BF (B), and 18F-BMS (C) in rats. Rats were intravenously injected with 5 MBq of 18F-BCPP-EF, 18F-BCPP-BF, or 18F-BMS via tail vein and sacrificed 1, 5, 10, 30, and 60 min after injection to calculate SUV. All values are expressed as mean ± SD for 3 animals.

  • FIGURE 2.
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    FIGURE 2.

    Effects of preadministration of rotenone on uptake of 18F-BCPP-EF (A), 18F-BCPP-BF (B), and 18F-BMS (C) in rats imaged by small-animal PET and X-CT. After continuous infusion of vehicle or rotenone at dose of 0.1 mg/kg/h for 1 h, PET scanning was conducted for 60 min after injection of each PET probe. Summation PET data from 10 to 30 min for A, B, and C were reconstructed for SUV images, and then PET images were superimposed on individual X-CT images.

  • FIGURE 3.
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    FIGURE 3.

    Effects of preadministration of rotenone on time–activity curves of 18F-BCPP-EF (A), 18F-BCPP-BF (B), and 18F-BMS (C) in rat brain. PET scans were conducted as described in Figure 2, and then summation data from 10 to 30 min were reconstructed for SUV images. ROIs for brain were set on reconstructed PET images to obtain time–activity curves of each PET probe in these regions. ○ = cortex-vehicle; ● = cortex-rotenone; △ = striatum-vehicle; ▲ = striatum-rotenone; □ = cerebellum-vehicle; ■ = cerebellum-rotenone.

  • FIGURE 4.
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    FIGURE 4.

    Effects of preadministration of rotenone on time–activity curves of 18F-BCPP-EF (A), 18F-BCPP-BF (B), and 18F-BMS (C) in rat heart. PET scans were conducted as described in Figure 2, and then summation data from 10 to 30 min were reconstructed for SUV images. ROIs for heart (myocardium) were set on reconstructed PET images to obtain time–activity curves of each PET probe in these regions. ○ = vehicle; ● = rotenone.

  • FIGURE 5.
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    FIGURE 5.

    Temporal changes in PET images of 18F-FDG and 18F-BCPP-EF in rat brains of PIT model. PET scans were conducted for 60 min with each PET probe before (normal), 1 (day 1), and 7 d (day 7) after PIT operation.

  • FIGURE 6.
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    FIGURE 6.

    Temporal changes in uptake (SUV ratio) of 18F-FDG and 18F-BCPP-EF in rat brains of PIT model. PET scans were conducted for 60 min with each PET probe before (normal), 1 (day 1), and 7 d (day 7) after PIT operation. #P < 0.01 vs. corresponding normal condition. $P < 0.01 vs. corresponding day 1 condition.

  • FIGURE 7.
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    FIGURE 7.

    Immunohistochemical analyses in rat brains of PIT model. Brains were dissected at day 7 for immunohistochemistry with Iba1 for inflammation and NeuN for neurons.

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    TABLE 1

    Uptake Ratios of Brain to Blood, Brain to Plasma, Heart to Blood, and Heart to Plasma of 18F-BCPP-EF, 18F-BCPP-BF, and 18F-BMS in Rat

    Probe1 min5 min10 min30 min60 min
    18F-BCPP-EF
     Brain to blood7.643 ± 0.49515.058 ± 1.35815.525 ± 2.1787.866 ± 0.4534.411 ± 0.435
     Brain to plasma5.280 ± 0.21711.703 ± 1.36111.879 ± 1.5595.941 ± 0.5023.328 ± 0.642
     Heart to blood26.785 ± 1.38754.629 ± 3.59663.098 ± 6.22641.310 ± 4.12524.705 ± 1.546
     Heart to plasma18.554 ± 1.69940.049 ± 1.85348.291 ± 4.32831.229 ± 3.95018.638 ± 1.245
    18F-BCPP-BF
     Brain to blood4.432 ± 0.37113.362 ± 1.32112.567 ± 0.70814.817 ± 3.15614.978 ± 3.006
     Brain to plasma3.926 ± 0.31910.986 ± 1.04210.039 ± 0.78611.658 ± 2.91811.112 ± 2.304
     Heart to blood19.617 ± 0.68065.826 ± 5.41872.429 ± 1.70376.204 ± 3.90983.791 ± 18.636
     Heart to plasma17.391 ± 1.02054.127 ± 4.27257.818 ± 2.27159.739 ± 5.14862.153 ± 14.094
    18F-BMS
     Brain to blood5.483 ± 1.28911.318 ± 1.32811.568 ± 2.9166.141 ± 0.3993.169 ± 0.124
     Brain to plasma4.291 ± 1.0308.804 ± 1.1169.039 ± 2.3294.657 ± 0.1282.511 ± 0.119
     Heart to blood25.195 ± 4.43856.286 ± 5.31953.204 ± 8.71429.393 ± 2.99614.379 ± 0.442
     Heart to plasma19.720 ± 3.65843.831 ± 5.40041.555 ± 6.98222.268 ± 1.42211.385 ± 0.172
    • Rats were intravenously injected with 5 MBq of 18F-BCPP-EF, 18F-BCPP-BF, or 18F-BMS via tail vein and sacrificed at 1, 5, 10, 30, and 60 min after injection to obtain tissue samples for uptake ratio analyses. All values are expressed as mean ± SD for 3 animals.

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    TABLE 2

    Metabolic Profiles of 18F-BCPP-EF, 18F-BCPP-BF, and 18F-BMS in Rat Brain and Plasma

    Probe1 min5 min10 min30 min60 min
    18F-BCPP-EF
     BrainND98.5 ± 0.1ND90.5 ± 0.284.4 ± 0.1
     Plasma84.5 ± 3.246.1 ± 8.040.4 ± 4.817.3 ± 2.68.3 ± 0.9
    18F-BCPP-BF
     BrainND99.3 ± 0.1ND97.1 ± 0.195.3 ± 0.1
     Plasma92.5 ± 0.369.5 ± 1.639.8 ± 2.018.4 ± 3.512.1 ± 3.6
    18F-BMS
     BrainND97.9 ± 0.3ND87.2 ± 0.576.3 ± 1.2
     Plasma89.8 ± 1.539.9 ± 3.524.3 ± 9.37.5 ± 1.82.9 ± 0.7
    • Rats were intravenously injected with 5 MBq of 18F-BCPP-EF, 18F-BCPP-BF, or 18F-BMS via tail vein and sacrificed at 1, 5, 10, 30, and 60 min after injection to obtain brain and plasma for metabolic analyses. All values are expressed as mean ± SD for 3 animals.

    • ND = not determined.

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Journal of Nuclear Medicine: 55 (3)
Journal of Nuclear Medicine
Vol. 55, Issue 3
March 1, 2014
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Novel PET Probes 18F-BCPP-EF and 18F-BCPP-BF for Mitochondrial Complex I: A PET Study in Comparison with 18F-BMS-747158-02 in Rat Brain
Hideo Tsukada, Shingo Nishiyama, Dai Fukumoto, Masakatsu Kanazawa, Norihiro Harada
Journal of Nuclear Medicine Mar 2014, 55 (3) 473-480; DOI: 10.2967/jnumed.113.125328

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Novel PET Probes 18F-BCPP-EF and 18F-BCPP-BF for Mitochondrial Complex I: A PET Study in Comparison with 18F-BMS-747158-02 in Rat Brain
Hideo Tsukada, Shingo Nishiyama, Dai Fukumoto, Masakatsu Kanazawa, Norihiro Harada
Journal of Nuclear Medicine Mar 2014, 55 (3) 473-480; DOI: 10.2967/jnumed.113.125328
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