Effects of a partial volume correction on [18F]florbetaben PET for the assessment of longitudinal β-amyloid load in APP-Swe mice

Objectives We previously investigated the progression of amyloid-β deposition in brain of mice over-expressing amyloid-precursor protein (APP-Swe), a model of Alzheimer’s disease (AD), in a longitudinal PET study with the novel amyloid-β tracer [18F]florbetaben (1). Signal loss due to partial volume effects is a well known problem especially in microPET studies, therefore we aimed to investigate corrections for partial volume effects (PVC).

Methods First in a phantom study using cannula filled with cross-calibrated activity the full-width-at-half-maximum (FWHM) of our Siemens Inveon DPET was assessed. Subsequently a volume-of-interest (VOI)-based PVC algorithm (2) using the appropriate FWHM was applied on in vivo microPET data. Therefore 90 min dynamic emission recordings were acquired following administration of [18F]florbetaben. A total of 32 PET scans in groups of APP-Swe (N=8) and age-matched wild-type (WT) mice (N=8) at 13 and 16 months were performed. After spatial normalization, VOI-based cortex-to-cerebellum ratios (SUVR) were calculated. Results of the VOI-based PVC algorithm were compared to uncorrected quantitation.

Results The phantom study revealed a FWHM of 1.72 mm. Without PVC cortical SUVR increased over time in APP-Swe mice compared to baseline estimates (+6.0%; p<0.05) or age-matched WT mice (+5.7%; p<0.05). The PVC increased mean cortical SUV by 65.8%, while mean cerebellar SUV increased by 33.3%. SUVR increased within groups longitudinally by 10.1% (p<0.01) compared to baseline and by 10.6% (p<0.01) compared to WT mice.

Conclusions The application of PVC to the currently largest dataset of the novel β-amyloid tracer [18F]florbetaben in an AD mouse model revealed increased group differences which might be specially suited for longitudinal studies. As statistical thresholds shifted towards higher significance levels, PVC improves the APP-Swe model in detecting early amyloidogenesis more sensitively.

Research Support Florbetaben precurser was provided by Piramal. APP-Swe mice were provided by F. Hoffmann-La Roche.