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

Abstract

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). [(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. 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. 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.