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European Journal of Nuclear Medicine and Molecular Imaging

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01.11.2012 | Original Article

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

verfasst von: Anniina Snellman, Johanna Rokka, Francisco R. Lopez-Picon, Olli Eskola, Ian Wilson, Gill Farrar, Mika Scheinin, Olof Solin, Juha O. Rinne, Merja Haaparanta-Solin

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 11/2012

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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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Titel: Pharmacokinetics of [18F]flutemetamol in wild-type rodents and its binding to beta amyloid deposits in a mouse model of Alzheimer’s disease
verfasst von: Anniina Snellman
Johanna Rokka
Francisco R. Lopez-Picon
Olli Eskola
Ian Wilson
Gill Farrar
Mika Scheinin
Olof Solin
Juha O. Rinne
Merja Haaparanta-Solin
Publikationsdatum: 01.11.2012
Verlag: Springer-Verlag
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 11/2012
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-012-2178-9

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

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