@article{4042abbc76b7442792e76cec7bc7ed2a,
title = "PET imaging of amyloid with Florbetapir F 18 and PET imaging of dopamine degeneration with 18F-AV-133 (florbenazine) in patients with Alzheimer's disease and Lewy body disorders",
abstract = "Background: Biomarkers based on the underlying pathology of Alzheimer's disease (AD) and Dementia with Lewy Bodies (DLB) have the potential to improve diagnosis and understanding of the substrate for cognitive impairment in these disorders. The objective of this study was to compare the patterns of amyloid and dopamine PET imaging in patients with AD, DLB and Parkinson's disease (PD) using the amyloid imaging agent florbetapir F 18 and 18F-AV-133 (florbenazine), a marker for vesicular monamine type 2 transporters (VMAT2).Methods: Patients with DLB and AD, Parkinson's disease (PD) and healthy controls (HC) were recruited for this study. On separate days, subjects received intravenous injections of florbetapir, and florbenazine. Amyloid burden and VMAT2 density were assessed quantitatively and by binary clinical interpretation. Imaging results for both tracers were compared across the four individual diagnostic groups and for combined groups based on underlying pathology (AD/DLB vs. PD/HC for amyloid burden and PD/DLB vs. AD/HC for VMAT binding) and correlated with measures of cognition and parkinsonism.Results: 11 DLB, 10 AD, 5 PD, and 5 controls participated in the study. Amyloid binding was significantly higher in the combined AD/DLB patient group (n = 21) compared to the PD/HC groups (n = 10, mean SUVr: 1.42 vs. 1.07; p = 0.0006). VMAT2 density was significantly lower in the PD/DLB group (n = 16) compared to the AD/ HC group (n = 15; 1.83 vs. 2.97; p < 0.0001). Within the DLB group, there was a significant correlation between cognitive performance and striatal florbenazine binding (r = 0.73; p = 0.011).Conclusions: The results of this study show significant differences in both florbetapir and florbenazine imaging that are consistent with expected pathology. In addition, VMAT density correlated significantly with cognitive impairment in DLB patients (ClinicalTrials.gov identifier: NCT00857506, registered March 5, 2009).",
keywords = "Alzheimer's disease, Biomarkers, PET imaging, Parkinson's disease",
author = "Andrew Siderowf and Pontecorvo, {Michael J.} and Shill, {Holly A.} and Mintun, {Mark A.} and Anupa Arora and Joshi, {Abhinay D.} and Ming Lu and Adler, {Charles H.} and Douglas Galasko and Carolyn Liebsack and Skovronsky, {Daniel M.} and Sabbagh, {Marwan N.}",
note = "Funding Information: No medical writer was used. The study was supported by a Research Grant by Avid Radiopharmaceuticals and the Banner Sun Health Research Institute. The Banner Sun Health Research Institute Brain Donation Program is supported by the National Institute of Aging (P30 AG19610 Arizona Alzheimer{\textquoteright}s Disease Core Center), the Arizona Department of Health Services (contract 211002, Arizona Alzheimer{\textquoteright}s Research Center), the Arizona Biomedical Research Commission (contracts 4001, 0011, and 05–901 to the Arizona Parkinson{\textquoteright}s Disease Consortium), and the Michael J. Fox Foundation for Parkinson{\textquoteright}s Research. The Avid co-investigators do not receive extramural funding. All other investigators are employed by BSHRI, or Mayo or UCSD. BSHRI was the grantee (through a contract) from Avid. None of the investigators were directly remunerated by the sponsor. Funding Information: Andrew Siderowf, Michael J. Pontecorvo, Mark A. Mintun, Anupa Arora, Abhinay D. Joshi, Ming Lu and Daniel M. Skovronsky are employed by Avid Radiopharmaceuticals, a subsidiary of Eli Lilly & Co. Dr. Holly A Shill has research support from Schering-Plough/Merck, Avid Radiopharmaceuticals, UCB Biosciences, Adamas Pharmaceuticals, International Essential Tremor Foundation, Michael J Fox Foundation for Parkinson Research, US Department of Defense and National Institutes of Health. Charles H. Adler Consultant: Xenoport, Impax, Teva, Ipsen, and Merz. Research support from the Arizona Biomedical Research Commission (contracts 4001, 0011, 05–901 and 1001 to the Arizona Parkinson{\textquoteright}s Disease Consortium), the National Institute of Neurological Disorders and Stroke (U24 NS072026 National Brain and Tissue Resource for Parkinson{\textquoteright}s Disease and Related Disorders), the Michael J. Fox Foundation for Parkinson{\textquoteright}s Research, the Mayo Clinic Foundation, Avid Radiopharmaceuticals, and Phytopharm. Douglas Galasko Dr. Galasko serves as Editor of Alzheimer1s Disease Research and Treatment; serves on Data Safety Monitoring Boards for Elan, Janssen and Balance Pharmaceuticals; is a consultant for Elan Pharmaceuticals. He receives research support from the NIH, the Michael J Fox Foundation and the Alzheimer1s Drug Discovery Foundation. Carolyn Liebsack has nothing to disclose. Marwan N. Sabbagh Grants/ Contracts: Pfizer, Eisai, Neuronix, Lilly, Avid, Piramal, GE, Avanir, Elan, Functional Neuromodulation, Advisory: Biogen, Lilly, Piramal, Eisai; Royalties: Wiley, Tenspeed (RandomHouse). Funding Information: This study (AV133-B03 (ClinicalTrials.gov identifier: NCT00857506) was sponsored by Avid Radiopharmaceuticals (a subsidiary of Eli Lilly and Co.). The study was approved by the Institutional Review Boards (IRB) at the University of Pennsylvania, University of California at San Diego and Banner Sun Health Research Institute. Written informed consent was obtained from study participants and/or their authorized representatives prior to conduct of any study procedures. The study consisted of a screening visit and two imaging visits. Screening assessments included demographic information, safety assessment, including clinical laboratory assessment, vital signs and ECG, and an MRI scan. Each subject was imaged on 2 separate sessions not more than 4 weeks apart.",
year = "2014",
month = apr,
day = "9",
doi = "10.1186/1471-2377-14-79",
language = "English (US)",
volume = "14",
journal = "BMC neurology",
issn = "1471-2377",
publisher = "BioMed Central",
number = "1",
}