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Biodistribution and Radiation Dosimetry for the Novel SV2A Radiotracer [18F]UCB-H: First-in-Human Study

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Abstract

Purpose

[18F]UCB-H is a novel radiotracer with a high affinity for synaptic vesicle glycoprotein 2A (SV2A), a protein expressed in synaptic vesicles. SV2A is the binding site of levetiracetam, a “first-in-class” antiepileptic drug with a distinct but still poorly understood mechanism of action. The objective of this study was to determine the biodistribution and radiation dosimetry of [18F]UCB-H in a human clinical trial and to establish injection limits according to biomedical research guidelines. Additionally, the clinical radiation dosimetry results were compared to estimations in previously published preclinical data.

Procedures

Dynamic whole body positron emission tomography/X-ray computed tomography (PET/CT) imaging was performed over approximately 110 min on five healthy male volunteers after injection of 144.5 ± 7.1 MBq (range, 139.1–156.5 MBq) of [18F]UCB-H. Major organs were delineated on CT images, and time–activity curves were obtained from co-registered dynamic PET emission scans. The bladder could only be delineated on PET images. Time-integrated activity coefficients were calculated as area under the curve using trapezoidal numerical integration. Urinary excretion data based on PET activities including voiding was also simulated using the dynamic bladder module of OLINDA/EXM. The radiation dosimetry was calculated using OLINDA/EXM.

Results

The effective dose to the OLINDA/EXM 70-kg standard male was 1.54 × 10−2 ± 6.84 × 10−4 millisieverts (mSv)/MBq, with urinary bladder wall, gallbladder wall, and the liver receiving the highest absorbed dose. The brain, the tracer’s main organ of interest, received an absorbed dose of 1.89 × 10−2 ± 2.32 × 10−3 mGy/MBq.

Conclusions

This first human dosimetry study of [18F]UCB-H indicated that the tracer shows similar radiation burdens to widely used common clinical tracers. Single injections of at maximum 672 MBq for US practice and 649 MBq for European practice keep radiation exposure below recommended limits. Recently published preclinical dosimetry data extrapolated from mice provided satisfactory prediction of total body and effective dose but showed significant differences in organ absorbed doses compared to human data.

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Acknowledgments

This work was funded by the Walloon Region Public Private Partnership NEUROCOM, with the University of Liège and UCB Pharma as partners. F. Bretin is supported by Marie Curie Initial Training Network (MCITN) “Methods in Neuroimaging” under Grant No. #MC-ITN-238593. M.A. Bahri is a “collaborateur logistique” and A. Plenevaux is a senior research associate from FRS-FNRS Belgium. We also acknowledge the comments of the reviewers, which helped to improve the contents of this article.

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Authors and Affiliations

  1. Cyclotron Research Centre, University of Liège, Allée du 6 Août, Sart Tilman B30, 4000, Liège, Belgium

    F. Bretin, M. A. Bahri, G. Warnock, J. Aerts, F. Mievis, F. Giacomelli, C. Degueldre, A. Luxen, A. Seret, A. Plenevaux & E. Salmon

  2. UCB Pharma, Braine l’Alleud, Belgium

    N. Mestdagh, T. Buchanan, C. Otoul & F. Koestler

  3. Nuclear Medicine, CHU, University of Liège, Liège, Belgium

    C. Bernard & R. Hustinx

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Corresponding author

Correspondence to E. Salmon.

Additional information

A. Plenevaux and E. Salmon contributed equally to this work.

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Bretin, F., Bahri, M.A., Bernard, C. et al. Biodistribution and Radiation Dosimetry for the Novel SV2A Radiotracer [18F]UCB-H: First-in-Human Study. Mol Imaging Biol 17, 557–564 (2015). https://doi.org/10.1007/s11307-014-0820-6

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