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Quantification of [18F]UCB-H Binding in the Rat Brain: From Kinetic Modelling to Standardised Uptake Value

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Abstract

Purpose

[18F]UCB-H is a specific positron emission tomography (PET) biomarker for the Synaptic Vesicle protein 2A (SV2A), the binding site of the antiepileptic drug levetiracetam. With a view to optimising acquisition time and simplifying data analysis with this radiotracer, we compared two parameters: the distribution volume (Vt) obtained from Logan graphical analysis using a Population-Based Input Function, and the Standardised Uptake Value (SUV).

Procedures

Twelve Sprague Dawley male rats, pre-treated with three different doses of levetiracetam were employed to develop the methodology. Three additional kainic acid (KA) treated rats (temporal lobe epilepsy model) were also used to test the procedure. Image analyses focused on: (i) length of the dynamic acquisition (90 versus 60 min); (ii) correlations between Vt and SUV over 20-min consecutive time-frames; (iii) and (iv) evaluation of differences between groups using the Vt and the SUV; and (v) preliminary evaluation of the methodology in the KA epilepsy model.

Results

A large correlation between the Vt issued from 60 to 90-min acquisitions was observed. Further analyses highlighted a large correlation (r > 0.8) between the Vt and the SUV. Equivalent differences between groups were detected for both parameters, especially in the 20–40 and 40–60-min time-frames. The same results were also obtained with the epilepsy model.

Conclusions

Our results enable the acquisition setting to be changed from a 90-min dynamic to a 20-min static PET acquisition. According to a better image quality, the 20–40-min time-frame appears optimal. Due to its equivalence to the Vt, the SUV parameter can be considered in order to quantify [18F]UCB-H uptake in the rat brain. This work, therefore, establishes a starting point for the simplification of SV2A in vivo quantification with [18F]UCB-H, and represents a step forward to the clinical application of this PET radiotracer.

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Acknowledgments

We would like to thank Miguel Manuel de Villena for the English revision of the manuscript. The authors are grateful to the Nucleis ULiège spin-off technicians for their help producing [18F]UCB-H.

Funding

This work was funded by University of Liège grant 13/17-07 and UCB BioPharma as partners. MES is supported by ULiege ARC 13/17 07 grant. AP is research director from FRS-FNRS Belgium.

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Authors and Affiliations

  1. GIGA – CRC In Vivo Imaging, University of Liège, Allée du 6 Août, Building B30, Sart Tilman, 4000, Liège, Belgium

    Maria Elisa Serrano, Mohamed Ali Bahri, Guillaume Becker, Alain Seret, Christian Lemaire, Eric Salmon, André Luxen & Alain Plenevaux

  2. Nucleis, University of Liège, Allée du 6 Août, Building B30, Sart Tilman, 4000, Liège, Belgium

    Frédéric Mievis & Fabrice Giacomelli

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  1. Maria Elisa Serrano
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  2. Mohamed Ali Bahri
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  3. Guillaume Becker
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  5. Frédéric Mievis
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  8. Eric Salmon
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Correspondence to Maria Elisa Serrano.

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The authors declare that they have no conflict of interest.

Ethical Approval

All animal experiments were performed according to the Helsinki declaration and conducted in accordance with the European guidelines for care of laboratory animals (2010/63/EU). All procedures were reviewed and approved by the Institutional Animal Care and Use Ethics Committee of the University of Liege, Belgium.

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Serrano, M.E., Bahri, M.A., Becker, G. et al. Quantification of [18F]UCB-H Binding in the Rat Brain: From Kinetic Modelling to Standardised Uptake Value. Mol Imaging Biol 21, 888–897 (2019). https://doi.org/10.1007/s11307-018-1301-0

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