Limitations of small animal PET imaging with [18F]FDDNP and FDG for quantitative studies in a transgenic mouse model of Alzheimer's disease.

Abstract

PURPOSE:

We evaluated the usefulness of small animal brain positron emission tomography (PET) imaging with the amyloid-beta (A beta) probe 2-(1-{6-[(2-[(18)F]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malonitrile ([(18)F]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:

[(18)F]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 [(18)F]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 [(18)F]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 [(18)F]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.

• Authors: Claudia Kuntner, Adam L Kesner, Martin Bauer, Robert Kremslehner, Thomas Wanek, Markus Mandler, Rudolf Karch, Johann Stanek, Tanja Wolf, Markus Müller, Oliver Langer
• Journal: Molecular imaging and biology (Mol Imaging Biol) 2009 Jul-Aug Vol. 11 Issue 4 Pg. 236-40 ISSN: 1860-2002 [Electronic] United States
• PMID: 19214638 (Publication Type: Journal Article)

Chemical References

• 2-(1-(6-((2-fluoroethyl)(methyl)amino)-2-naphthyl)ethylidene)malononitrile
• Amyloid beta-Peptides
• Nitriles
• Radiopharmaceuticals
• Fluorodeoxyglucose F18

Topics

• Alzheimer Disease (diagnostic imaging, pathology)
• Amyloid beta-Peptides (metabolism)
• Animals
• Brain (diagnostic imaging, pathology)
• Brain Chemistry
• Disease Models, Animal
• Fluorodeoxyglucose F18 (pharmacokinetics)
• Imaging, Three-Dimensional (methods)
• Mice
• Mice, Transgenic
• Nitriles (pharmacokinetics)
• Phantoms, Imaging
• Positron-Emission Tomography (methods)
• Radiopharmaceuticals (pharmacokinetics)
• Statistics, Nonparametric