Authors: Henryk Barthel Julia Luthardt Georg Becker Marianne Patt Eva Hammerstein Kristin Hartwig Birk Eggers Bernhard Sattler Andreas Schildan Swen Hesse Philipp M Meyer Henrike Wolf Torsten Zimmermann Joachim Reischl Beate Rohde HermannJosef Gertz Cornelia Reininger Osama Sabri
Publish Date: 2011/05/06
Volume: 38, Issue: 9, Pages: 1702-1714
Abstract
Complementing clinical findings with those generated by biomarkers—such as βamyloidtargeted positron emission tomography PET imaging—has been proposed as a means of increasing overall accuracy in the diagnosis of Alzheimer’s disease AD Florbetaben 18FBAY 949172 is a novel βamyloid PET tracer currently in global clinical development We present the results of a proof of mechanism study in which the diagnostic efficacy pharmacokinetics safety and tolerability of florbetaben were assessed The value of various quantitative parameters derived from the PET scans as potential surrogate markers of cognitive decline was also investigatedTen patients with mildmoderate probable AD DSMIV and NINCDSADRDA criteria and ten agematched ≥ 55 years healthy controls HCs were administered a single dose of 300 MBq florbetaben which contained a tracer mass dose of 5 μg The 70–90 min postinjection brain PET data were visually analysed by three blinded experts Quantitative assessment was also performed via MRIbased anatomical sampling of predefined volumes of interest VOI and subsequent calculation of standardized uptake value SUV ratios SUVRs cerebellar cortex as reference region Furthermore singlecase voxelwise analysis was used to calculate individual “whole brain βamyloid load”Visual analysis of the PET data revealed nine of the ten AD but only one of the ten HC brains to be βamyloid positive p = 0001 with high interreader agreement weighted kappa ≥ 088 When compared to HCs the neocortical SUVRs were significantly higher in the ADs with descending order of effect size in frontal cortex lateral temporal cortex occipital cortex anterior and posterior cingulate cortices and parietal cortex p = 0003–0010 Voxelbased group comparison confirmed these differences Amongst the PETderived parameters the Statistical Parametric Mappingbased whole brain βamyloid load yielded the closest correlation with the MiniMental State Examination scores r = −0736 p 0001 following a nonlinear regression curve No serious adverse events or other safety concerns were seenThese results indicate florbetaben to be a safe and efficacious βamyloidtargeted tracer with favourable brain kinetics Subjects with AD could be easily differentiated from HCs by both visual and quantitative assessment of the PET data The operatorindependent voxelbased analysis yielded whole brain βamyloid load which appeared valuable as a surrogate marker of disease severityWe would like to thank all patients their caregivers and the healthy volunteers who participated in this trial Further the support of the PET and cyclotron teams of the Department of Nuclear Medicine University of Leipzig is greatly acknowledged This trial was supported by Bayer Healthcare Berlin Germany
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