Amyloid PET imaging in Alzheimer’s disease: a comparison of three radiotracers
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The increasing use of amyloid PET in Alzheimer’s disease research and clinical trials has motivated efforts to standardize methodology. We compared retention of the 11C radiotracer Pittsburgh Compound B (PiB) and that of two 18F amyloid radiotracers (florbetapir and flutemetamol) using two study populations. We also examined the feasibility of converting between tracer-specific measures, using PiB as the common link between the two 18F tracers.
One group of 40 subjects underwent PiB and flutemetamol imaging sessions and a separate group of 32 subjects underwent PiB and florbetapir imaging sessions. We compared cortical and white matter retention for each 18F tracer relative to that of PiB, as well as retention in several reference regions and image analysis methods. Correlations between tracer pairs were used to convert tracer-specific threshold values for amyloid positivity between tracers.
Cortical retention for each pair of tracers was strongly correlated regardless of reference region (PiB–flutemetamol, ρ = 0.84–0.99; PiB–florbetapir, ρ = 0.83–0.97) and analysis method (ρ = 0.90–0.99). Compared to PiB, flutemetamol had higher white matter retention, while florbetapir had lower cortical retention. Two previously established independent thresholds for amyloid positivity were highly consistent when values were converted between tracer pairs.
Despite differing white and grey matter retention characteristics, cortical retention for each 18F tracer was highly correlated with that of PiB, enabling conversion of thresholds across tracer measurement scales with a high level of internal consistency. Standardization of analysis methods and measurement scales may facilitate the comparison of amyloid PET data obtained using different tracers.
KeywordsAmyloid Alzheimer’s disease PET imaging Neurology
We thank Robert Koeppe, Abhinay Joshi, and Cindee Madison for helpful discussions and assistance with image analysis.
B.T. acknowledges the support of GlaxoSmithKline (GSK) and also that UCL/UCLH receives a portion of its research funding from the UK Department of Health Biomedical Research Centre’s funding scheme.
Data collection and sharing for this project was funded by the ADNI (National Institutes of Health grant U01 AG024904). ADNI is funded by the National Institute on Aging, and the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott; Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Amorfix Life Sciences Ltd.; AstraZeneca; Bayer HealthCare; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research provides funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129 and K01 AG030514.
Conflicts of interest
S.M. Landau has previously consulted for Avid Radiopharmaceuticals, Inc., Janssen Alzheimer Immunotherapy, and Biogen Idec.
B.A. Thomas has performed research under a grant partially supported by GE Healthcare.
L. Thurfjell is an employee of GE Healthcare.
M. Schmidt is an employee of Janssen Research and Development.
R. Margolin is an employee of Janssen Alzheimer Immunotherapy R&D LLC.
M. Pontecorvo and M. Mintun are employees of Avid Radiopharmaceuticals, Inc.
W.J. Jagust collaborates with Avid Radiopharmaceuticals, Inc. through participation in the ADNI. He has previously consulted for GE Healthcare, Genentech, and Elan/Janssen Alzheimer Immunotherapy, and is currently a consultant to F. Hoffman-LaRoche and Synarc.
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