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Pharmacokinetics of [18F]flutemetamol in wild-type rodents and its binding to beta amyloid deposits in a mouse model of Alzheimer’s disease

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

The aim of this study was to investigate the potential of [18F]flutemetamol as a preclinical PET tracer for imaging β-amyloid (Aβ) deposition by comparing its pharmacokinetics to those of [11C]Pittsburgh compound B ([11C]PIB) in wild-type Sprague Dawley rats and C57Bl/6N mice. In addition, binding of [18F]flutemetamol to Aβ deposits was studied in the Tg2576 transgenic mouse model of Alzheimer’s disease.

Methods

[18F]Flutemetamol biodistribution was evaluated using ex vivo PET methods and in vivo PET imaging in wild-type rats and mice. Metabolism and binding of [11C]PIB and [18F]flutemetamol to plasma proteins were analysed using thin-layer chromatography and ultrafiltration methods, respectively. Radiation dose estimates were calculated from rat ex vivo biodistribution data. The binding of [18F]flutemetamol to Aβ deposits was also studied using ex vivo and in vitro autoradiography. The location of Aβ deposits in the brain was determined with thioflavine S staining and immunohistochemistry.

Results

The pharmacokinetics of [18F]flutemetamol resembled that of [11C]PIB in rats and mice. In vivo studies showed that both tracers readily entered the brain, and were excreted via the hepatobiliary pathway in both rats and mice. The metabolism of [18F]flutemetamol into radioactive metabolites was faster than that of [11C]PIB. [18F]Flutemetamol cleared more slowly from the brain than [11C]PIB, particularly from white matter, in line with its higher lipophilicity. Effective dose estimates for [11C]PIB and [18F]flutemetamol were 2.28 and 6.65 μSv/MBq, respectively. Autoradiographs showed [18F]flutemetamol binding to fibrillar Aβ deposits in the brain of Tg2576 mice.

Conclusion

Based on its pharmacokinetic profile, [18F]flutemetamol showed potential as a PET tracer for preclinical imaging. It showed good brain uptake and was bound to Aβ deposits in the brain of Tg2576 mice. However, its high lipophilicity might complicate the analysis of PET data, particularly in small-animal imaging.

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Acknowledgments

The authors wish to thank the staff of the Accelerator Laboratory for radionuclide production, the staff of the Radiopharmaceutical Chemistry Laboratory for radiotracer production, and Tarja Marttila, Leena Tokoi-Eklund, Elisa Riuttala, and Marko Vehmanen for assistance in animal studies. The study was supported financially by clinical grants from Turku University Hospital (project 13464), the Academy of Finland (project 17652), the Sigrid Jusélius Foundation and the EU 6th Framework Project ADIT (contract number 511977), which is gratefully acknowledged.

Author information

Authors and Affiliations

  1. MediCity/PET Preclinical Laboratory, Turku PET Centre, University of Turku, Tykistökatu 6A, FI-20520, Turku, Finland

    Anniina Snellman, Francisco R. Lopez-Picon & Merja Haaparanta-Solin

  2. Radiopharmaceutical Chemistry Laboratory, Turku PET Centre, University of Turku, Turku, Finland

    Johanna Rokka, Olli Eskola & Olof Solin

  3. Accelerator Laboratory, Turku PET Centre, Åbo Akademi University, Turku, Finland

    Olof Solin

  4. Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland

    Juha O. Rinne

  5. GE Healthcare Medical Diagnostics, Little Chalfont, Buckinghamshire, UK

    Ian Wilson & Gill Farrar

  6. Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland

    Mika Scheinin

  7. Unit of Clinical Pharmacology, Turku University Hospital, Turku, Finland

    Mika Scheinin

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  1. Anniina Snellman
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  2. Johanna Rokka
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  9. Juha O. Rinne
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Corresponding author

Correspondence to Merja Haaparanta-Solin.

Additional information

Anniina Snellman and Johanna Rokka contributed equally to this work.

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Snellman, A., Rokka, J., Lopez-Picon, F.R. et al. Pharmacokinetics of [18F]flutemetamol in wild-type rodents and its binding to beta amyloid deposits in a mouse model of Alzheimer’s disease. Eur J Nucl Med Mol Imaging 39, 1784–1795 (2012). https://doi.org/10.1007/s00259-012-2178-9

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  • DOI: https://doi.org/10.1007/s00259-012-2178-9

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