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Limitations of Small Animal PET Imaging with [18F]FDDNP and FDG for Quantitative Studies in a Transgenic Mouse Model of Alzheimer’s Disease

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Abstract

Purpose

We evaluated the usefulness of small animal brain positron emission tomography (PET) imaging with the amyloid-beta (Aβ) probe 2-(1-{6-[(2-[18F]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malonitrile ([18F]FDDNP) and with 2-deoxy-2-[F-18]fluoro-d-glucose (FDG) for detection and quantification of pathological changes occurring in a transgenic mouse model of Alzheimer’s disease (Tg2576 mice).

Procedures

[18F]FDDNP (n = 6) and FDG-PET scans (n = 3) were recorded in Tg2576 mice (age 13–15 months) and age-matched wild-type litter mates. Brain volumes of interest were defined by co-registration of PET images with a 3D MOBY digital mouse phantom. Regional [18F]FDDNP retention in mouse brain was quantified in terms of the relative distribution volume (DVR) using Logan’s graphical analysis with cerebellum as a reference region.

Results

Except for a lower maximum brain uptake of radioactivity in transgenic animals, the regional brain kinetics as well as DVR values of [18F]FDDNP appeared to be similar in both groups of animals. Also for FDG, regional radioactivity retention was almost identical in the brains of transgenic and control animals.

Conclusions

We could not detect regionally increased [18F]FDDNP binding and regionally decreased FDG binding in the brains of Tg2576 transgenic versus wild-type mice. However, small group differences in signal might have been masked by inter-animal variability. In addition, technical limitations of the applied method (partial volume effect, spatial resolution) for measurements in such small organs as mouse brain have to be taken into consideration.

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Acknowledgments

The authors wish to thank the staff of the Department of Radiopharmaceuticals for the preparation of FDG and for technical assistance with the radiosynthesis of [18F]FDDNP. Maria Zsebedics from the Department of Toxicology is gratefully acknowledged for helping with the handling of laboratory animals and Peter Angelberger and Herbert Kvaternik for continuous support and scientific advice. Vladimir Kepe (UCLA) is acknowledged for advice regarding the analysis of [18F]FDDNP microPET data.

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Authors and Affiliations

  1. Department of Radiopharmaceuticals & microPET Imaging, Austrian Research Centers GmbH—ARC, 2444, Seibersdorf, Austria

    Claudia Kuntner, Robert Kremslehner, Thomas Wanek, Johann Stanek & Oliver Langer

  2. Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria

    Martin Bauer, Markus Müller & Oliver Langer

  3. Department of Toxicology, Austrian Research Centers GmbH—ARC, 2444, Seibersdorf, Austria

    Tanja Wolf

  4. AFFiRiS GmbH, Vienna, Austria

    Markus Mandler

  5. Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA

    Adam L. Kesner

  6. Institute of Solid State Physics, University of Technology, Vienna, Austria

    Robert Kremslehner

  7. Department of Medical Computer Sciences, Medical University of Vienna, Vienna, Austria

    Rudolf Karch

Authors
  1. Claudia Kuntner
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  2. Adam L. Kesner
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  3. Martin Bauer
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  4. Robert Kremslehner
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  5. Thomas Wanek
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  6. Markus Mandler
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  7. Rudolf Karch
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  8. Johann Stanek
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  9. Tanja Wolf
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  10. Markus Müller
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  11. Oliver Langer
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Corresponding author

Correspondence to Claudia Kuntner.

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Kuntner, C., Kesner, A.L., Bauer, M. et al. Limitations of Small Animal PET Imaging with [18F]FDDNP and FDG for Quantitative Studies in a Transgenic Mouse Model of Alzheimer’s Disease. Mol Imaging Biol 11, 236–240 (2009). https://doi.org/10.1007/s11307-009-0198-z

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  • DOI: https://doi.org/10.1007/s11307-009-0198-z

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