[P‐114]: In vivo [F‐18]FDDNP microPET imaging of brain B‐amyloid in a transgenic rat model of Alzheimer's disease
Vladimir Kepe, Gregory M. Cole, Jie Liu, Dorothy G. Flood, Stephen P. Trusko, Nagichettiar Satyamurthy, Sung-Chen Huang, Gary W. Small, Michael E. Phelps, Jorge R. Barrio · Alzheimer s & Dementia · 2005
Molecular imaging is increasingly gaining importance in research on Alzheimer's disease (AD). Development of probes labeling the pathological lesion found in AD in recent years and availability of the rodent models of AD gave us the unique opportunity to study pathological processes in AD in vivo. We have applied [F-18]FDDNP, a molecular probe with binding affinity for β-amyloid and tau deposits, for imaging of the brain pathology in a new triple transgenic rat model of β-amyloidosis in AD, recently developed by Cephalon, Inc. and Xenogen Biosciences. The objective of this work was to detect and to quantitate the levels of β-amyloid deposition in these triple transgenic rats using [F-18]FDDNP microPET. Concorde Focus microPET camera was used to perform sixty minute scans on three triple transgenic rats (15 months old) and on two control Sprague-Dawley rats (9 months old). After normalization and FBP reconstruction the resulting dynamic images were used to generate the distribution volume (DV) parametric images using Logan plot graphical analysis with cerebellum as reference region. The parametric images were used for the quantitative analysis. The results of three [F-18]FDDNP microPET scans in control animals (one rat was scanned twice) show almost uniform distribution of binding in the cortical regions and cerebellum (DV: frontal 1.04± 0.01; hippocampus 0.99±0.04, normalized to cerebellum). As expected, five scans performed on transgenic animals (two rats were scanned twice) show elevated binding in several cortical regions when compared with cerebellum (DV: frontal 1.32±0.04, p<0.0005; hippocampus 1.23±0.05, p=0.001) but not in subcortical regions or white matter. This cortical [F-18]FDDNP binding in transgenic rats can be abolished by pre-treatment with (S)-naproxen. These results demonstrate that [F-18]FDDNP is a useful probe for in vivo microPET detection of brain β-amyloid load in the triple transgenic rat model of amyloid deposition. These results open the opportunity for longitudinal monitoring of the progression of brain pathology in the living animals and for studying the effectiveness of new therapeutic treatment approaches targeting β-amyloid. The rat model is also a powerfull tool for screening and evaluation of new molecular probes for β-amyloid aggregates.