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Research ArticleBasic Science Investigations

Evaluation of 18F-UCB-H as a Novel PET Tracer for Synaptic Vesicle Protein 2A in the Brain

Geoffrey I. Warnock, Joël Aerts, Mohamed Ali Bahri, Florian Bretin, Christian Lemaire, Fabrice Giacomelli, Frederic Mievis, Nathalie Mestdagh, Tim Buchanan, Anne Valade, Joël Mercier, Martyn Wood, Michel Gillard, Alain Seret, André Luxen, Eric Salmon and Alain Plenevaux
Journal of Nuclear Medicine August 2014, 55 (8) 1336-1341; DOI: https://doi.org/10.2967/jnumed.113.136143
Geoffrey I. Warnock
1Cyclotron Research Centre, University of Liège, Liège, Belgium; and
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Joël Aerts
1Cyclotron Research Centre, University of Liège, Liège, Belgium; and
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Mohamed Ali Bahri
1Cyclotron Research Centre, University of Liège, Liège, Belgium; and
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Florian Bretin
1Cyclotron Research Centre, University of Liège, Liège, Belgium; and
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Christian Lemaire
1Cyclotron Research Centre, University of Liège, Liège, Belgium; and
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Fabrice Giacomelli
1Cyclotron Research Centre, University of Liège, Liège, Belgium; and
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Frederic Mievis
1Cyclotron Research Centre, University of Liège, Liège, Belgium; and
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Nathalie Mestdagh
2UCB Pharma, Brussels, Belgium
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Tim Buchanan
2UCB Pharma, Brussels, Belgium
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Anne Valade
2UCB Pharma, Brussels, Belgium
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Joël Mercier
2UCB Pharma, Brussels, Belgium
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Martyn Wood
2UCB Pharma, Brussels, Belgium
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Michel Gillard
2UCB Pharma, Brussels, Belgium
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Alain Seret
1Cyclotron Research Centre, University of Liège, Liège, Belgium; and
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André Luxen
1Cyclotron Research Centre, University of Liège, Liège, Belgium; and
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Eric Salmon
1Cyclotron Research Centre, University of Liège, Liège, Belgium; and
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Alain Plenevaux
1Cyclotron Research Centre, University of Liège, Liège, Belgium; and
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  • FIGURE 1.
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    FIGURE 1.

    Overview of 18F-UCB-H synthesis (17). Reagents and conditions: a = N-tetradecyltrimethylammonium+18F-F−/tetraethylammonium+HCO3− in dimethyl sulfoxide–N,N-dimethylformamide (16), 140°C, 2 min; b = triethylamine-methanol, 60°C, 20 min; c and d = NaBH4, 60°C, 25 min. Et = ethyl group.

  • FIGURE 2.
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    FIGURE 2.

    Brain uptake of 18F-UCBH after blockade with successive doses of LEV (average uptake over 60 min). %ID = percentage injected dose.

  • FIGURE 3.
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    FIGURE 3.

    Time–activity curves for 18F-UCBH uptake in representative regions, with β-microprobe–derived whole-blood input function (IF) and corrected AIF (corrected for plasma-to-whole blood ratio and plasma parent fraction with population-based corrections). %ID = percentage injected dose.

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    FIGURE 4.

    Parent fraction curve (♦; mean ± SD; n = 4; solid line represents biexponential fit) used for correction of AIF for tracer metabolism in vivo. Additional data points (jittered for legibility) show parent fraction after LEV pretreatment (n = 4 or 5 in each group; ○, 0.1 mg/kg; △, 1 mg/kg; ●, 10 mg/kg; ▲, 100 mg/kg).

  • FIGURE 5.
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    FIGURE 5.

    Example of Logan graphic analysis of 18F-UCB-H binding in hippocampal region. Main plot: ○, data points excluded from fit; ●, data points included in fit; solid line represents fit. Subplot: fit residuals.

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    TABLE 1

    Vt in Controls (n = 4), Reproducibility of Vt, and Blocking of 18F-UCB-H Binding by LEV

    Blocking of 18F-UCB-H binding by LEV at‡:
    Brain regionVt (mL/cm3)*Reproducibility of Vt†0.1 mg/kg1 mg/kg10 mg/kg100 mg/kg
    Nucleus accumbens10.9 ± 0.53.3 ± 15.0−7.3 ± 1.4−16.3 ± 7.1−35.2 ± 20.4−53.2 ± 9.0§
    Amygdala9.0 ± 0.33.9 ± 13.6−8.7 ± 5.3−16.0 ± 8.1−33.0 ± 24.4−49.0 ± 11.3§
    Cerebellum9.0 ± 0.22.2 ± 13.3−7.4 ± 3.9−15.6 ± 7.5−30.2 ± 23.7−43.8 ± 8.4ǁ
    Cerebral cortex9.4 ± 0.43.6 ± 12.8−10.3 ± 6.0−16.3 ± 8.4−33.0 ± 20.5−48.6 ± 9.2ǁ
    Striatum11.3 ± 0.53.3 ± 14.5−7.6 ± 4.0−17.1 ± 6.1−35.1 ± 20.2−53.5 ± 9.8§
    Hippocampus10.7 ± 0.53.3 ± 14.3−9.2 ± 5.4−15.7 ± 7.1−34.1 ± 22.2−52.6 ± 11.6§
    Hypothalamus9.9 ± 0.23.3 ± 13.2−9.9 ± 1.3−16.4 ± 7.7−36.8 ± 23.3−54.2 ± 9.0§
    Medulla8.5 ± 0.43.2 ± 12.1−8.1 ± 4.5−15.3 ± 7.1−28.3 ± 17.5−34.4 ± 9.2ǁ
    Olfactory bulbs9.0 ± 0.24.4 ± 12.0−6.8 ± 2.5−15.0 ± 7.1−27.4 ± 22.3−41.9 ± 9.2ǁ
    Pons8.2 ± 0.35.2 ± 12.4−14.1 ± 0.2−15.9 ± 5.4−29.3 ± 8.7ǁ−35.2 ± 11.7§
    Septum10.5 ± 0.44.6 ± 18.4−6.9 ± 6.6−16.9 ± 7.0−33.4 ± 21.7−50.8 ± 10.0ǁ
    Thalamus12.1 ± 0.62.5 ± 14.0−10.8 ± 4.3−16.1 ± 5.7−36.2 ± 21.5−55.8 ± 10.3§
    Whole-brain average9.8 ± 0.53.6 ± 13.1−9.0 ± 4.6−13.3 ± 3.3−25.7 ± 28.0−43.8 ± 4.7ǁ
    • ↵* Determined by Logan graphic analysis and reported as mean ± SD.

    • ↵† Determined as percentage difference in test–retest study and reported as mean ± SD.

    • ↵‡ Determined by Logan graphic analysis as percentage change in Vt in test–retest study and reported as mean ± SD.

    • ↵§ P value, determined by 1-way ANOVA and Tukey post hoc test, was less than 0.01.

    • ↵ǁ P value, determined by 1-way ANOVA and Tukey post hoc test, was less than 0.05.

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Journal of Nuclear Medicine: 55 (8)
Journal of Nuclear Medicine
Vol. 55, Issue 8
August 1, 2014
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Evaluation of 18F-UCB-H as a Novel PET Tracer for Synaptic Vesicle Protein 2A in the Brain
Geoffrey I. Warnock, Joël Aerts, Mohamed Ali Bahri, Florian Bretin, Christian Lemaire, Fabrice Giacomelli, Frederic Mievis, Nathalie Mestdagh, Tim Buchanan, Anne Valade, Joël Mercier, Martyn Wood, Michel Gillard, Alain Seret, André Luxen, Eric Salmon, Alain Plenevaux
Journal of Nuclear Medicine Aug 2014, 55 (8) 1336-1341; DOI: 10.2967/jnumed.113.136143

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Evaluation of 18F-UCB-H as a Novel PET Tracer for Synaptic Vesicle Protein 2A in the Brain
Geoffrey I. Warnock, Joël Aerts, Mohamed Ali Bahri, Florian Bretin, Christian Lemaire, Fabrice Giacomelli, Frederic Mievis, Nathalie Mestdagh, Tim Buchanan, Anne Valade, Joël Mercier, Martyn Wood, Michel Gillard, Alain Seret, André Luxen, Eric Salmon, Alain Plenevaux
Journal of Nuclear Medicine Aug 2014, 55 (8) 1336-1341; DOI: 10.2967/jnumed.113.136143
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