Amyloid imaging in cognitively normal older adults: comparison between 18F-flutemetamol and 11C-Pittsburgh compound B
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Preclinical, or asymptomatic, Alzheimer’s disease (AD) refers to the presence of positive AD biomarkers in the absence of cognitive deficits. This research concept is being applied to define target populations for clinical drug development. In a prospective community-recruited cohort of cognitively intact older adults, we compared two amyloid imaging markers within subjects: 18F-flutemetamol and 11C-Pittsburgh compound B (PIB).
In 32 community-recruited cognitively intact older adults aged between 65 and 80 years, we determined the concordance between binary classification based on 18F-flutemetamol versus 11C-PIB according to semiquantitative assessment (standardized uptake value ratio in composite cortical volume, SUVRcomp) and, alternatively, according to visual reads. We also determined the correlation between 18F-flutemetamol and 11C-PIB SUVR and evaluated how this was affected by the reference region chosen (cerebellar grey matter versus pons) and the use of partial volume correction (PVC) in this population.
Binary classification based on semiquantitative assessment was concordant between 18F-flutemetamol and 11C-PIB in 94 % of cases. Concordance of blinded binary visual reads between tracers was 84 %. The Spearman correlation between 18F-flutemetamol and 11C-PIB SUVRcomp with cerebellar grey matter as reference region was 0.84, with a slope of 0.98. Correlations in neocortical regions were significantly lower with the pons as reference region. PVC improved the correlation in striatum and medial temporal cortex.
For the definition of preclinical AD based on 18F-flutemetamol, concordance with 11C-PIB was highest using semiquantitative assessment with cerebellar grey matter as reference region.
KeywordsAmyloid PET Biomarker Alzheimer’s disease Preclinical AD
We would like to thank the staff of Nuclear Medicine, Neurology, and Radiology at the University Hospitals Leuven. Special thanks to Carine Schildermans, Dorien Timmers, Kwinten Porters and Mieke Steukers for help with the study.
Compliance with ethical standards
This study was funded by the Foundation for Alzheimer Research SAO-FRMA (grant numbers 09013, 11020, 13007); Research Foundation Flanders (grant number G.0660.09); KU Leuven (grant numbers OT/08/056, OT/12/097); IWT VIND; IWT TGO BioAdapt AD; Belspo IAP (grant number P7/11); Research Foundation Flanders senior clinical investigator grant to R.V. and K.V.L.; Research Foundation Flanders doctoral fellowship to K.A; and KH is supported by the Research Fund KU Leuven (grant numbers OT/11/087 and CREA/14/023). 18F-Flutemetamol was provided by GE Healthcare free of charge for this academic investigator-driven trial.
Conflicts of interest
Katarzyna Adamczuk, Jolien Schaeverbeke, Natalie Nelissen, Veerle Neyens, Mathieu Vandenbulcke, Karolien Goffin, Johan Lilja, Kelly Hilven, Patrick Dupont and Koen Van Laere declare that they have no conflicts of interest. Rik Vandenberghe was the PI of the phase 1 and 2 18F-flutemetamol trials. UZ Leuven has had a clinical trial agreement for these trials with GE Healthcare. RV has a consultancy agreement with GE Healthcare. 18F-Flutemetamol was provided by GE Healthcare for the conduct of reported investigator-driven trial free of cost.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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