Molecular Imaging and Biology

, Volume 11, Issue 4, pp 236–240 | Cite as

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

  • Claudia KuntnerEmail author
  • Adam L. Kesner
  • Martin Bauer
  • Robert Kremslehner
  • Thomas Wanek
  • Markus Mandler
  • Rudolf Karch
  • Johann Stanek
  • Tanja Wolf
  • Markus Müller
  • Oliver Langer
Brief Article



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).


[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.


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.


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.

Key words

Alzheimer’s disease (AD) PET [18F]FDDNP FDG Transgenic mouse Amyloid-beta (Aβ) 



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.


  1. 1.
    Nordberg A (2007) Amyloid imaging in Alzheimer's disease. Curr Opin Neurol 20:398–402PubMedCrossRefGoogle Scholar
  2. 2.
    Klunk WE, Engler H, Nordberg A et al (2004) Imaging brain amyloid in Alzheimer's disease with Pittsburgh compound-B. Ann Neurol 55:306–319PubMedCrossRefGoogle Scholar
  3. 3.
    Price JC, Klunk WE, Lopresti BJ et al (2005) Kinetic modeling of amyloid binding in humans using PET imaging and Pittsburgh compound-B. J Cereb Blood Flow Metab 25:1528–1547PubMedCrossRefGoogle Scholar
  4. 4.
    Klunk WE, Wang Y, Huang GF et al (2003) The binding of 2-(4′-methylaminophenyl)benzothiazole to postmortem brain homogenates is dominated by the amyloid component. J Neurosci 23:2086–2092PubMedGoogle Scholar
  5. 5.
    Agdeppa ED, Kepe V, Liu J et al (2003) 2-Dialkylamino-6-acylmalononitrile substituted naphthalenes (DDNP analogs): novel diagnostic and therapeutic tools in Alzheimer’s disease. Mol Imaging Biol 5:404–417PubMedCrossRefGoogle Scholar
  6. 6.
    Lockhart A (2006) Imaging Alzheimer’s disease pathology: one target, many ligands. Drug Discov Today 11:1093–1099PubMedCrossRefGoogle Scholar
  7. 7.
    Shoghi-Jadid K, Small GW, Agdeppa ED et al (2002) Localization of neurofibrillary tangles and beta-amyloid plaques in the brains of living patients with Alzheimer disease. Am J Geriatr Psychiatry 10:24–35PubMedGoogle Scholar
  8. 8.
    Small GW, Kepe V, Ercoli LM et al (2006) PET of brain amyloid and tau in mild cognitive impairment. N Engl J Med 355:2652–2663PubMedCrossRefGoogle Scholar
  9. 9.
    Mosconi L, De Santi S, Rusinek H, Convit A, de Leon MJ (2004) Magnetic resonance and PET studies in the early diagnosis of Alzheimer’s disease. Expert Rev Neurother 4:831–849PubMedCrossRefGoogle Scholar
  10. 10.
    Schenk D, Barbour R, Dunn W et al (1999) Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 400:173–177PubMedCrossRefGoogle Scholar
  11. 11.
    Churcher I, Beher D (2005) Gamma-secretase as a therapeutic target for the treatment of Alzheimer’s disease. Curr Pharm Des 11:3363–3382PubMedCrossRefGoogle Scholar
  12. 12.
    Klunk WE, Lopresti BJ, Ikonomovic MD et al (2005) Binding of the positron emission tomography tracer Pittsburgh compound-B reflects the amount of amyloid-beta in Alzheimer’s disease brain but not in transgenic mouse brain. J Neurosci 25:10598–10606PubMedCrossRefGoogle Scholar
  13. 13.
    Toyama H, Ye D, Ichise M et al (2005) PET imaging of brain with the beta-amyloid probe, [11C]6-OH-BTA-1, in a transgenic mouse model of Alzheimer’s disease. Eur J Nucl Med Mol Imaging 32:593–600PubMedCrossRefGoogle Scholar
  14. 14.
    Ye LA, Morgenstern JL, Lamb JR, Lockhart A (2006) Characterisation of the binding of amyloid imaging tracers to rodent A beta fibrils and rodent–human A beta co-polymers. Biochem Biophys Res Commun 347:669–677PubMedCrossRefGoogle Scholar
  15. 15.
    Maeda J, Ji B, Irie T et al (2007) Longitudinal, quantitative assessment of amyloid, neuroinflammation, and anti-amyloid treatment in a living mouse model of Alzheimer’s disease enabled by positron emission tomography. J Neurosci 27:10957–10968PubMedCrossRefGoogle Scholar
  16. 16.
    Kepe V, Cole GM, Liu J et al (2005) Visualization of beta-amyloid deposits in the living brain of a triple transgenic rat model of beta-amyloid deposition using [18F]FDDNP-microPET imaging. J Labelled Compd Rad 48:S43 (symposium abstract)Google Scholar
  17. 17.
    Liu J, Kepe V, Zabjek A et al (2007) High-yield, automated radiosynthesis of 2-(1-{6-[(2-[(18)F]Fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malono nitrile ([(18)F]FDDNP) ready for animal or human administration. Mol Imaging Biol 9:6–16PubMedCrossRefGoogle Scholar
  18. 18.
    Matise MP, Joyner AL (1997) Expression patterns of developmental control genes in normal and Engrailed-1 mutant mouse spinal cord reveal early diversity in developing interneurons. J Neurosci 17:7805–7816PubMedGoogle Scholar
  19. 19.
    Kremslehner R, Gurker N, Kesner AL, Kuntner C (2007) Computer-assisted localization of mice organs in micro positron emission tomography. Nuklearmedizin 46:A159 (symposium abstract)Google Scholar
  20. 20.
    Kesner AL, Dahlbom M, Huang SC et al (2006) Semiautomated analysis of small-animal PET data. J Nucl Med 47:1181–1186PubMedGoogle Scholar
  21. 21.
    Logan J, Fowler JS, Volkow ND et al (1996) Distribution volume ratios without blood sampling from graphical analysis of PET data. J Cereb Blood Flow Metab 16:834–840PubMedCrossRefGoogle Scholar
  22. 22.
    Reiman EM, Uecker A, Gonzalez-Lima F et al (2000) Tracking Alzheimer’s disease in transgenic mice using fluorodeoxyglucose autoradiography. Neuroreport 11:987–991PubMedCrossRefGoogle Scholar
  23. 23.
    Valla J, Schneider L, Reiman EM (2006) Age- and transgene-related changes in regional cerebral metabolism in PSAPP mice. Brain Res 1116:194–200PubMedCrossRefGoogle Scholar
  24. 24.
    Van Dam D, De Deyn PP (2006) Drug discovery in dementia: the role of rodent models. Nat Rev Drug Discov 5:956–970PubMedCrossRefGoogle Scholar

Copyright information

© Academy of Molecular Imaging 2009

Authors and Affiliations

  • Claudia Kuntner
    • 1
    Email author
  • Adam L. Kesner
    • 5
  • Martin Bauer
    • 2
  • Robert Kremslehner
    • 1
    • 6
  • Thomas Wanek
    • 1
  • Markus Mandler
    • 4
  • Rudolf Karch
    • 7
  • Johann Stanek
    • 1
  • Tanja Wolf
    • 3
  • Markus Müller
    • 2
  • Oliver Langer
    • 1
    • 2
  1. 1.Department of Radiopharmaceuticals & microPET ImagingAustrian Research Centers GmbH—ARCSeibersdorfAustria
  2. 2.Department of Clinical PharmacologyMedical University of ViennaViennaAustria
  3. 3.Department of ToxicologyAustrian Research Centers GmbH—ARCSeibersdorfAustria
  4. 4.AFFiRiS GmbHViennaAustria
  5. 5.Department of Molecular and Medical Pharmacology, David Geffen School of MedicineUCLALos AngelesUSA
  6. 6.Institute of Solid State PhysicsUniversity of TechnologyViennaAustria
  7. 7.Department of Medical Computer SciencesMedical University of ViennaViennaAustria

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