In Vivo Imaging of Amyloid Deposition in Alzheimer Disease Using the Radioligand 18 F-AV-45 (Flobetapir F 18)
Open accessAbstract
UNLABELLED: An (18)F-labeled PET amyloid-beta (Abeta) imaging agent could facilitate the clinical evaluation of late-life cognitive impairment by providing an objective measure for Alzheimer disease (AD) pathology. Here we present the results of a clinical trial with (E)-4-(2-(6-(2-(2-(2-(18)F-fluoroethoxy)ethoxy)ethoxy)pyridin-3-yl)vinyl)-N-methyl benzenamine ((18)F-AV-45 or florbetapir [corrected] F 18). METHODS: An open-label, multicenter brain imaging, metabolism, and safety study of (18)F-AV-45 was performed on 16 patients with AD (Mini-Mental State Examination score, 19.3 +/- 3.1; mean age +/- SD, 75.8 +/- 9.2 y) and 16 cognitively healthy controls (HCs) (Mini-Mental State Examination score, 29.8 +/- 0.45; mean age +/- SD, 72.5 +/- 11.6 y). Dynamic PET was performed over a period of approximately 90 min after injection of the tracer (370 MBq [10 mCi]). Standardized uptake values and cortical-to-cerebellum standardized uptake value ratios (SUVRs) were calculated. A simplified reference tissue method was used to generate distribution volume ratio (DVR) parametric maps for a subset of subjects. RESULTS: Valid PET data were available for 11 AD patients and 15 HCs. (18)F-AV-45 accumulated in cortical regions expected to be high in Abeta deposition (e.g., precuneus and frontal and temporal cortices) in AD patients; minimal accumulation of the tracer was seen in cortical regions of HCs. The cortical-to-cerebellar SUVRs in AD patients showed continual substantial increases through 30 min after administration, reaching a plateau within 50 min. The 10-min period from 50 to 60 min after administration was taken as a representative sample for further analysis. The cortical average SUVR for this period was 1.67 +/- 0.175 for patients with AD versus 1.25 +/- 0.177 for HCs. Spatially normalized DVRs generated from PET dynamic scans were highly correlated with SUVR (r = 0.58-0.88, P < 0.005) and were significantly greater for AD patients than for HCs in cortical regions but not in subcortical white matter or cerebellar regions. No clinically significant changes in vital signs, electrocardiogram, or laboratory values were observed. CONCLUSION: (18)F-AV-45 was well tolerated, and PET showed significant discrimination between AD patients and HCs, using either a parametric reference region method (DVR) or a simplified SUVR calculated from 10 min of scanning 50-60 min after (18)F-AV-45 administration.
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Amyloid imaging biomarkers were available for 54 individuals in the UCSF cohort, and all were positive.
“Amyloid imaging biomarkers, obtained via positron emission tomography imaging with Pittsburgh compound B (11C-PiB)24 or Florbetapir F 18 (18F-AV-45)25 were available for 54 individuals, and all were positive.”
From Whole-genome sequencing suggests a chemokine gene cluster that modifies age at onset in familial Alzheimer's disease (2015) · cites this paper as [25]
Positron emission tomography ligands have been shown to provide a minimally invasive estimate of the neuropathological features of Alzheimer disease, such as amyloid-β neuritic plaque deposition.
“Positron emission tomography (PET) ligands have been shown to provide a minimally invasive estimate of the neuropathological features of AD, such as Aβ neuritic plaque deposition.15,16,17,18”
From Positron Emission Tomography Imaging With [ <sup>18</sup> F]flortaucipir and Postmortem Assessment of Alzheimer Disease Neuropathologic Changes (2020) · cites this paper as [15]
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“When compared with the available data from the other 18F compounds (15,16), the effect size for 18Fflutemetamol (2.”
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“There are three (18)F-labelled ligands currently undergoing clinical trials: [(18)F]florbetapir [3], [(18)F]florbetaben [4] and [(18)F]flutemetamol [5].”
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“Three novel 18F tracers, 18Fflorbetapir, 18F-florbetaben, and 18F-flutemetamol (Wong et al., 2010; Villemagne et al., 2012; Rominger et al., 2013; Curtis et al., 2015) have extended the ability to use PET to monitor disease progression and amyloid accumulation.”
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“These are florbetaben (4,8,9), florbetapir (5,6), and flutemetamol (7).”
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Partial volume correction in quantitative amyloid imaging
Su, Y., Blazey, T. M., Snyder, A. Z., Raichle, M. E., Marcus, D. S., Ances, B. M., Bateman, R. J., Cairns, N. J., Aldea, P., Cash, L., et al. (2015) · NeuroImage · doi:10.1016/j.neuroimage.2014.11.058 · Cited by 247 · see citing works
“…(Aβ) plaques with tracers such as [11C]PiB (N-methyl-[11C]2-(4-methylaminophenyl)-6-hydroxybenzothiazole) (Klunk et al., 2004), [18F]florbetapir (Wong et al., 2010), [18F]florbetaben (Rowe et al., 2008) and [18F]flutemetamol (Vandenberghe et al., 2010), enables in vivo measurement of fibrillar…”
BackgroundClinical amyloid imaging in Alzheimer's disease
Herholz, K., & Ebmeier, K. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(11)70123-5 · Cited by 240 · see citing works
Navitsky, M., Joshi, A. D., Kennedy, I., Klunk, W. E., Rowe, C. C., Wong, D. F., Pontecorvo, M. J., Mintun, M. A., & Devous, M. D. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.06.1353 · Cited by 229 · see citing works
Self-citationBeta‐amyloid deposition and the aging brain
Rodrigue, K. M., Kennedy, K. M., & Park, D. C. (2009) · Neuropsychology Review · doi:10.1007/s11065-009-9118-x · Cited by 230 · see citing works
Thurfjell, L., Lilja, J., Lundqvist, R., Buckley, C. J., Smith, A. P. L., Vandenberghe, R. R., & Sherwin, P. F. (2014) · Journal of Nuclear Medicine · doi:10.2967/jnumed.114.142109 · Cited by 224 · see citing works
“At the time of writing, 18F-florbetapir (2,3) and 18F-florbetaben (4,5) are approved for clinical use by the Food and Drug Administration and the European Medicines Agency, and 18F-flutemetamol (6,7) is approved by the Food and Drug Administration and is under evaluation by the European Medicines Agency.”
BackgroundClinical Validation of 18 F-AZD4694, an Amyloid-β–Specific PET Radioligand
Cselényi, Z., Eriksdotter, M., Forsberg, A., Halldin, C., Julin, P., Schou, M., Johnström, P., Varnäs, K., Svensson, S., & Farde, L. (2012) · Journal of Nuclear Medicine · doi:10.2967/jnumed.111.094029 · Cited by 225 · see citing works
“Such presence of relatively high nonspecific binding in white matter has been observed also for other amyloid-b radioligands (11,12,31).”
BackgroundBiomarkers for the Early Detection and Progression of Alzheimer's Disease
Counts, S. E., Ikonomovic, M. D., Mercado, N., Vega, I. E., & Mufson, E. J. (2017) · Neurotherapeutics · doi:10.1007/s13311-016-0481-z · Cited by 224 · see citing works
On the early diagnosis of Alzheimer's Disease from multimodal signals: A survey
Alberdi, A., Aztiria, A., & Basarab, A. (2016) · Artificial Intelligence in Medicine · doi:10.1016/j.artmed.2016.06.003 · Cited by 222 · see citing works
Burnham, S. C., Bourgeat, P., Doré, V., Savage, G., Brown, B., Laws, S., Maruff, P., Salvado, O., Ames, D., Martins, R. N., et al. (2016) · The Lancet Neurology · doi:10.1016/s1474-4422(16)30125-9 · Cited by 207 · see citing works
Effect of amyloid on memory and non-memory decline from preclinical to clinical Alzheimer’s disease
Lim, Y. Y., Maruff, P. T., Pietrzak, R. H., Ames, D. J., Ellis, K. A., Harrington, K., Lautenschlager, N. T., Szoeke, C. E. I., Martins, R. N., Masters, C. L., et al. (2013) · Brain · doi:10.1093/brain/awt286 · Cited by 210 · see citing works
Rowe, C. C., Pejoska, S., Mulligan, R. S., Jones, G. R., Chan, J. G., Svensson, S., Cselényi, Z., Masters, C. L., & Villemagne, V. L. (2013) · Journal of Nuclear Medicine · doi:10.2967/jnumed.112.114785 · Cited by 193 · see citing works
Comparison of 11C-PiB and 18F-florbetaben for Aβ imaging in ageing and Alzheimer’s disease
Villemagne, V. L., Mulligan, R. S., Pejoska, S., Ong, K. T., Jones, G. R., O'Keefe, G. J., Chan, J. G., Young, K., Tochon‐Danguy, H., Masters, C. L., et al. (2012) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-012-2088-x · Cited by 190 · see citing works
González‐Escamilla, G., Lange, C., Teipel, S. J., Buchert, R., & Grothe, M. J. (2016) · NeuroImage · doi:10.1016/j.neuroimage.2016.12.077 · Cited by 186 · see citing works
“In any case, the module propagates the template space parcellation atlas of choice to the individual MRI and then limits the ROIs to the segmented GM tissue, thresholded at 50% gray matter probability (Firbank et al., 2008; Rodrigue et al., 2012; Sun et al., 2007; Wong et al., 2010).”
In vivo quantification of neurofibrillary tangles with [18F]MK-6240
Pascoal, T. A., Shin, M., Kang, M. S., Chamoun, M., Chartrand, D. A., Mathotaarachchi, S. S., Bennacef, I., Therriault, J., Ng, K. P., Hopewell, R., et al. (2018) · Alzheimer s Research & Therapy · doi:10.1186/s13195-018-0402-y · Cited by 185 · see citing works
Chandra, A., Valkimadi, P., Pagano, G., Cousins, O., Dervenoulas, G., Politis, M., & Initiative, A. D. N. (2019) · Human Brain Mapping · doi:10.1002/hbm.24782 · Cited by 185 · see citing works
“While 18F-labelled amyloid tracers are equivalent in their degree of diagnostic accuracy (Morris et al., 2016), [18F]florbetapir shows partic- ularly fast brain kinetics relative to others (Wong et al., 2010).”
BackgroundDevelopment of Positron Emission Tomography β-Amyloid Plaque Imaging Agents
Mathis, C. A., Mason, N. S., Lopresti, B. J., & Klunk, W. E. (2012) · Seminars in Nuclear Medicine · doi:10.1053/j.semnuclmed.2012.07.001 · Cited by 176 · see citing works
McBride, J. C., Zhao, X., Munro, N. B., Smith, C. D., Jicha, G. A., Hively, L. M., Broster, L. S., Schmitt, F. A., Kryscio, R. J., & Jiang, Y. (2014) · Computer Methods and Programs in Biomedicine · doi:10.1016/j.cmpb.2014.01.019 · Cited by 176 · see citing works
“The current leading hypothesis for the cause of AD is abnormal deposition of amyloid beta protein in the brain together with a second abnormal protein, microtubule-associated tau [4],[5].”
BackgroundPET amyloid-beta imaging in preclinical Alzheimer's disease
Vlassenko, A. G., Benzinger, T. L. S., & Morris, J. C. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.11.005 · Cited by 173 · see citing works
BODIPY-Based Molecular Probe for Imaging of Cerebral β-Amyloid Plaques
Ono, M., Watanabe, H., Kimura, H., & Saji, H. (2012) · ACS Chemical Neuroscience · doi:10.1021/cn3000058 · Cited by 164 · see citing works
Longitudinal Amyloid Imaging Using 11C-PiB: Methodologic Considerations
van Berckel, B. N. M., Ossenkoppele, R., Tolboom, N., Yaqub, M. M., Foster‐Dingley, J. C., Windhorst, A. D., Scheltens, P., Lammertsma, A. A., & Boellaard, R. (2013) · Journal of Nuclear Medicine · doi:10.2967/jnumed.112.113654 · Cited by 163 · see citing works
Characterizing Alzheimer's disease using a hypometabolic convergence index
Chen, K., Ayutyanont, N., Langbaum, J. B. S., Fleisher, A., Reschke, C., Lee, W., Liu, X., Bandy, D., Alexander, G. E., Thompson, P. M., et al. (2011) · NeuroImage · doi:10.1016/j.neuroimage.2011.01.049 · Cited by 160 · see citing works
“…(Aβ) PETmeasurements using Pittsburgh Compound B (PiB) (Ikonomovic et al., 2008; Klunk et al., 2004) or other recently developed radioligand (Wong et al., 2010) and cerebrospinal fluid (CSF) amyloidbeta1–42 (Aβ1–42) levels alone or in combinationwith total tau (t-tau) or phosphorylated…”
MethodPositron Emission Tomography in CNS Drug Discovery and Drug Monitoring
Piel, M., Vernaleken, I., & Rösch, F. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm5001858 · Cited by 156 · see citing works
The Relationship between Sleep Quality and Brain Amyloid Burden
Brown, B. M., Rainey‐Smith, S. R., Villemagne, V. L., Weinborn, M., Bucks, R. S., Sohrabi, H. R., Laws, S. M., Taddei, K., Macaulay, S. L., Ames, D. J., et al. (2016) · SLEEP · doi:10.5665/sleep.5756 · Cited by 158 · see citing works
Neuroimaging and Other Biomarkers for Alzheimer's Disease: The Changing Landscape of Early Detection
Risacher, S. L., & Saykin, A. J. (2013) · Annual Review of Clinical Psychology · doi:10.1146/annurev-clinpsy-050212-185535 · Cited by 155 · see citing works
“…(FDG), which measures brain metabolism (Jagust et al. 2010, Langbaum et al. 2009); and (b) amyloid tracers, including [11C]Pittsburgh compound B (PiB) and [18F]Florbetapir, which bind to fibrillar amyloid plaques (Klunk et al. 2004, Vandenberghe et al. 2010, Wong et al. 2010).”
BackgroundRajasekhar, K., & Govindaraju, T. (2018) · RSC Advances · doi:10.1039/c8ra03620a · Cited by 150 · see citing works
Sulfur [ 18 F]Fluoride Exchange Click Chemistry Enabled Ultrafast Late-Stage Radiosynthesis
Zheng, Q., Xu, H., Wang, H., Han, W., Wang, N., Xiong, H., Gu, Y., Noodleman, L., Sharpless, K. B., Yang, G., et al. (2021) · Journal of the American Chemical Society · doi:10.1021/jacs.0c09306 · Cited by 151 · see citing works
Multimodality Review of Amyloid-related Diseases of the Central Nervous System
Miller‐Thomas, M. M., Sipe, A. L., Benzinger, T. L. S., McConathy, J., Connolly, S., & Schwetye, K. E. (2016) · Radiographics · doi:10.1148/rg.2016150172 · Cited by 234 · see citing works
Disease Tracking Markers for Alzheimer's Disease at the Prodromal (MCI) Stage
Drago, V., Babiloni, C., David Bartrés-faz, A., Caroli, A., Bosch, B., Hensch, T., Didic, M., Klafki, H., Pievani, M., Jovicich, J., et al. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-0043 · Cited by 138 · see citing works
<scp>EFNS</scp> task force: the use of neuroimaging in the diagnosis of dementia
Filippi, M., Agosta, F., Barkhof, F., Dubois, B., Fox, N. C., Frisoni, G. B., Jack, C. R., Johannsen, P., Miller, B. L., Nestor, P. J., et al. (2012) · European Journal of Neurology · doi:10.1111/j.1468-1331.2012.03859.x · Cited by 141 · see citing works
Near-infrared fluorescent probes for imaging of amyloid plaques in Alzheimer׳s disease
Tong, H., Lou, K., & Wang, W. (2015) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2014.12.006 · Cited by 142 · see citing works
Standardized Expression of 18F-NAV4694 and 11C-PiB β-Amyloid PET Results with the Centiloid Scale
Rowe, C. C., Jones, G. R., Doré, V., Pejoska, S., Margison, L., Mulligan, R. S., Chan, J. G., Young, K., & Villemagne, V. L. (2016) · Journal of Nuclear Medicine · doi:10.2967/jnumed.115.171595 · Cited by 141 · see citing works
“Like 11C-PiB, 18F-NAV4694 has higher specific cortical binding and lower nonspecific white matter binding than has been reported for other 18F-labeled Ab radiopharmaceuticals (3,23,25,26).”
BackgroundComparison of Pittsburgh compound B and florbetapir in cross‐sectional and longitudinal studies
Su, Y., Flores, S. E., Wang, G., Hornbeck, R. C., Speidel, B. A., Joseph‐Mathurin, N., Vlassenko, A. G., Gordon, B. A., Koeppe, R. A., Klunk, W. E., et al. (2019) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2018.12.008 · Cited by 140 · see citing works
Amyloid tracers detect multiple binding sites in Alzheimer's disease brain tissue
Ni, R., Gillberg, P., Bergfors, A., Marutle, A., & Nordberg, A. K. (2013) · Brain · doi:10.1093/brain/awt142 · Cited by 134 · see citing works
Utilizing the Centiloid scale in cross-sectional and longitudinal PiB PET studies
Su, Y., Flores, S., Hornbeck, R. C., Speidel, B., Vlassenko, A. G., Gordon, B. A., Koeppe, R. A., Klunk, W. E., Xiong, C., Morris, J. C., et al. (2018) · NeuroImage: Clinical · doi:10.1016/j.nicl.2018.04.022 · Cited by 126 · see citing works
“…this goal, positron emission tomography (PET) imaging tracers such as [11C]Pittsburgh Compound-B (PiB) (Klunk et al., 2004), [18F]florbetapir (Wong et al., 2010), [18F]florbetaben (Rowe et al., 2008) and [18F]flutemetamol (Vandenberghe et al., 2010), were developed to enable in vivo…”
BackgroundThe Future of Precision Medicine in the Cure of Alzheimer’s Disease
Arafah, A., Khatoon, S., Rasool, I., Khan, A., Rather, M. A., Abujabal, K. A., Faqih, Y. A. H., Rashid, H., Rashid, S. M., Bilal Ahmad, S., et al. (2023) · Biomedicines · doi:10.3390/biomedicines11020335 · Cited by 133 · see citing works
Comparison of MR-less PiB SUVR quantification methods
Bourgeat, P., Villemagne, V. L., Doré, V., Brown, B. M., Macaulay, S. L., Martins, R. N., Masters, C. L., Ames, D. J., Ellis, K. A., Rowe, C. C., et al. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.04.033 · Cited by 127 · see citing works
“(Rowe et al., 2008; Wong et al., 2010, Vandenberghe et al., 2010) The analysis of PiB images requires accurate quantification of its retention in the brain.”
BackgroundAmyloid imaging as a biomarker for cerebral β-amyloidosis and risk prediction for Alzheimer dementia
Klunk, W. E. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.09.006 · Cited by 128 · see citing works
“, 2008)), [F-18]florbetapir (AV-45; (Wong et al., 2010)) and [F-18]flutemetamol (3’F-PiB or GE-067; (Nelissen et al.”
BackgroundFarrell, M. E., Jiang, S., Schultz, A. P., Properzi, M. J., Price, J. C., Becker, J. A., Jacobs, H. I. L., Hanseeuw, B. J., Rentz, D. M., Villemagne, V. L., et al. (2020) · Neurology · doi:10.1212/wnl.0000000000011214 · Cited by 129 · see citing works
Tartaglia, M. C., Rosen, H. J., & Miller, B. L. (2011) · Neurotherapeutics · doi:10.1007/s13311-010-0012-2 · Cited by 124 · see citing works
Regional amyloid accumulation and cognitive decline in initially amyloid-negative adults
Farrell, M. E., Chen, X., Rundle, M. M., Chan, M. Y., Wig, G. S., & Park, D. C. (2018) · Neurology · doi:10.1212/wnl.0000000000006469 · Cited by 126 · see citing works
Schmidt, M. E., Chiao, P., Klein, G., Matthews, D. C., Thurfjell, L., Cole, P. E., Margolin, R. A., Landau, S. M., Foster, N. L., Mason, N. S., et al. (2014) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2014.09.004 · Cited by 125 · see citing works
Lameka, K., Farwell, M. D., & Ichise, M. (2016) · Handbook of clinical neurology · doi:10.1016/b978-0-444-53485-9.00011-8 · Cited by 124 · see citing works
Sperling, R. A., Johnson, K. A., Doraiswamy, P. M., Reiman, E. M., Fleisher, A., Sabbagh, M. N., Sadowsky, C., Carpenter, A. P., Davis, M. D., Lu, M., et al. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.06.014 · Cited by 123 · see citing works
“A emiautomated technique was used for image quantification nd analysis as previously reported (Clark et al., 2011; leisher et al., 2011; Wong et al., 2010).”
MethodSelf-citationYao, J., Rettberg, J. R., Klosinski, L. P., Cadenas, E., & Brinton, R. D. (2011) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2011.10.005 · Cited by 124 · see citing works
“The most thoroughly studied examples of these compounds are Pittsburgh Compound B (PiB) (Klunk et al., 2004) and 18F-AV-45 (florbetapir) (Wong et al., 2010).”
BackgroundGrundman, M., Pontecorvo, M. J., Salloway, S., Doraiswamy, P. M., Fleisher, A., Sadowsky, C., Nair, A. K., Siderowf, A. D., Lu, M., Arora, A., et al. (2012) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0b013e318279d02a · Cited by 119 · see citing works
Self-citationWu, K.-Y., Hsiao, I., Chen, C., Chen, C., Hsieh, C., Wai, Y., Chang, C., Tseng, H., Yen, T.-C., Liu, C.-Y., et al. (2013) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-013-2627-0 · Cited by 121 · see citing works
“Because of its good tolerability and advantages (relatively long radioactive half-life, relatively rapid kinetics, and relatively long plateau), (18)F-florbetapir PET imaging might become a robust biomarker for imaging AD pathology [11].”
Manook, A., Yousefi, B. H., Willuweit, A., Platzer, S., Reder, S., Voß, A., Huisman, M. C., Settles, M., Neff, F., Velden, J., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031310 · Cited by 116 · see citing works
PRECISION MEDICINE - THE GOLDEN GATE FOR DETECTION, TREATMENT AND PREVENTION OF ALZHEIMER’S DISEASE
Hampel, H. J., O’Bryant, S. E., Castrillo, J. I., Ritchie, C. W., Rojkova, K., Broich, K., Benda, N., Nisticò, R., Frank, R., Dubois, B., et al. (2016) · The Journal of Prevention of Alzheimer s Disease · doi:10.14283/jpad.2016.112 · Cited by 116 · see citing works
Mormino, E. C., & Papp, K. V. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-179928 · Cited by 117 · see citing works
Nuclear imaging modalities for cardiac amyloidosis
Bokhari, S., Shahzad, R., Castaño, A., & Maurer, M. S. (2013) · Journal of Nuclear Cardiology · doi:10.1007/s12350-013-9803-2 · Cited by 114 · see citing works
Aβ-amyloid and Tau Imaging in Dementia
Villemagne, V. L., Doré, V., Bourgeat, P., Burnham, S. C., Laws, S., Salvado, O., Masters, C. L., & Rowe, C. C. (2017) · Seminars in Nuclear Medicine · doi:10.1053/j.semnuclmed.2016.09.006 · Cited by 110 · see citing works
Lundqvist, R., Lilja, J., Thomas, B. A., Lötjönen, J. M. P., Villemagne, V. L., Rowe, C. C., & Thurfjell, L. (2013) · Journal of Nuclear Medicine · doi:10.2967/jnumed.112.115006 · Cited by 110 · see citing works
“18F-florbetapir (2,3) has recently been approved in the United States, and compounds in late-stage development include the investigational amyloid imaging agents 18F-flutemetamol (4,5) and 18F-florbetaben (6,7).”
BackgroundSuppiah, S., Didier, M.-A., & Vinjamuri, S. (2019) · Diagnostics · doi:10.3390/diagnostics9020065 · Cited by 111 · see citing works
“It has a high affinity to aggregated Aβ, good separation between the radiotracer amyloid retention and background signal, and a long, stable pseudo-equilibrium allowing flexibility in the timing of image acquisition [29].”
BackgroundMethodTosun, D., Landau, S. M., Aisen, P. S. S., Petersen, R. C., Mintun, M. A., Jagust, W., Weiner, M. W., & Initiative, A. D. N. (2017) · Brain · doi:10.1093/brain/awx046 · Cited by 108 · see citing works
“…et al., 2013) and its relationship with antecedent and cross-sectional amyloid-b pathology as measured by florbetapir-PET retention longi- tudinally (Wong et al., 2010), as well as its relationship with other Alzheimer’s disease-related factors, using data from asymptomatic elderly individuals…”
BackgroundUzuegbunam, B. C., Librizzi, D., & Yousefi, B. H. (2020) · Molecules · doi:10.3390/molecules25040977 · Cited by 103 · see citing works
Ferreira, L. K., & Busatto, G. F. (2011) · Clinics · doi:10.1590/s1807-59322011001300003 · Cited by 102 · see citing works
“availability and allow short post-dose waiting periods and flexibility in timing of image acquisition.(44) Recent investigations have shown that (18)F-florbetapir PET imaging per-”
BackgroundToussaint, P., Maiz, S., Coynel, D., Doyon, J., Messé, A., de Souza, L. C., Sarazin, M., Perlbarg, V., Habert, M., & Benali, H. (2014) · NeuroImage · doi:10.1016/j.neuroimage.2014.08.003 · Cited by 100 · see citing works
Amyloid PET in clinical practice: Its place in the multidimensional space of Alzheimer's disease
Vandenberghe, R., Adamczuk, K., Dupont, P., Laere, K. V., & Chételat, G. (2013) · NeuroImage: Clinical · doi:10.1016/j.nicl.2013.03.014 · Cited by 99 · see citing works
“, 2008) and (18)F-florbetapir (Wong et al., 2010), and the naphthol (18)F-FDDNP (Small et al.”
BackgroundUsing Pittsburgh Compound B for In Vivo PET Imaging of Fibrillar Amyloid-Beta
Cohen, A. D., Rabinovici, G. D., Mathis, C. A., Jagust, W. J., Klunk, W. E., & Ikonomović, M. D. (2012) · Advances in pharmacology · doi:10.1016/b978-0-12-394816-8.00002-7 · Cited by 99 · see citing works
“A clinical trial performed on 18 mild-moderate AD patients (mean MMSE = 19.3) and 16 HCs showed that cortical regions had a higher [F-18]florbetapir retention, while white matter and cerebellar retention were not different between AD and control subjects (Wong et al., 2010).”
InfluentialPotential Therapies by Stem Cell‐Derived Exosomes in CNS Diseases: Focusing on the Neurogenic Niche
Luarte, A., Bátiz, L. F., Wyneken, Ú., & Lafourcade, C. (2016) · Stem Cells International · doi:10.1155/2016/5736059 · Cited by 99 · see citing works
“F-florbetapir, which presents a higher uptake inADpatients than controls [17] and has been recently approved by the FDA [18].”
Detecting earlier stages of amyloid deposition using PET in cognitively normal elderly adults
Guo, T., Landau, S. M., Jagust, W. J., & Initiative, A. D. N. (2020) · Neurology · doi:10.1212/wnl.0000000000009216 · Cited by 95 · see citing works
Estrogen Regulation of Mitochondrial Bioenergetics
Yao, J., & Brinton, R. D. (2012) · Advances in pharmacology · doi:10.1016/b978-0-12-394816-8.00010-6 · Cited by 97 · see citing works
“The most thoroughly studied examples of these compounds are Pittsburgh Compound B (PiB) (Klunk et al., 2004) and 18F-AV-45 (florbetapir) (Wong et al., 2010).”
BackgroundBiomarkers in Neurodegenerative Diseases
Jeromin, A., & Bowser, R. (2017) · Advances in Neurobiology · doi:10.1007/978-3-319-57193-5_20 · Cited by 92 · see citing works
Flortaucipir F 18 quantitation using parametric estimation of reference signal intensity.
Southekal, S., Devous, M. D., Kennedy, I., Navitsky, M., Lu, M., Joshi, A. D., Pontecorvo, M. J., & Mintun, M. A. (2018) · Journal of Nuclear Medicine · doi:10.2967/jnumed.117.200006 · Cited by 92 · see citing works
Self-citationA Semiautomated Method for Quantification of F 18 Florbetapir PET Images
Joshi, A. D., Pontecorvo, M. J., Lu, M., Skovronsky, D., Mintun, M. A., & Devous, M. D. (2015) · Journal of Nuclear Medicine · doi:10.2967/jnumed.114.153494 · Cited by 92 · see citing works
“However, the SPM2 analysis of 11 AD subjects acquired as part of a previous study (10) identified higher accumulation of F 18 Florbetapir in 6 of these regions (medial orbital frontal, temporal, parietal, anterior cingulate, posterior cingulate, and precuneus), which were also expected to have high accumulation of Ab…”
BackgroundMethodInfluentialSelf-citationPositron Emission Tomography Radiopharmaceuticals for Imaging Brain Beta-Amyloid
Vallabhajosula, S. (2011) · Seminars in Nuclear Medicine · doi:10.1053/j.semnuclmed.2011.02.005 · Cited by 90 · see citing works
Signs and Artifacts in Amyloid PET
Lundeen, T. F., Seibyl, J. P., Covington, M. F., Eshghi, N., & Kuo, P. H. (2018) · Radiographics · doi:10.1148/rg.2018180160 · Cited by 91 · see citing works
Bettcher, B. M., Fitch, R., Wynn, M. J., Lalli, M. A., Elofson, J., Jastrzab, L., Mitic, L., Miller, Z. A., Rabinovici, G. D., Miller, B. L., et al. (2016) · Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring · doi:10.1016/j.dadm.2016.05.004 · Cited by 89 · see citing works
Rostomian, A. H., Madison, C. M., Rabinovici, G. D., & Jagust, W. J. (2011) · Journal of Nuclear Medicine · doi:10.2967/jnumed.110.082057 · Cited by 89 · see citing works
- Authors
- Wong, D. F., Rosenberg, P. B., Zhou, Y., Kumar, A., Raymont, V., Ravert, H. T., Dannals, R. F., Nandi, A., Brašić, J. R., Ye, W., Hilton, J., Lyketsos, C., Kung, H. F., Joshi, A. D., Skovronsky, D. M., & Pontecorvo, M. J.
- Affiliations
- Johns Hopkins University (US)
- University of Pennsylvania (US)
- Eli Lilly (United States) (US)
- ORCID
- Venue
- Journal of Nuclear Medicine
- Publisher
- Society of Nuclear Medicine
- Published
- 2010-05-25
- Volume
- 51
- Issue
- 6
- Pages
- 913-920
- ISSN
- 0161-5505 (ISSN-L)
- 2159-662X
- PMC
- PMC3101877
- OpenAlex
- W2040174321
- Cited by
- 684
- References
- 35
- Citations by year
- 2026: 21 · 2025: 22 · 2024: 17 · 2023: 25 · 2022: 32 · 2021: 42 · 2020: 43 · 2019: 31 · 2018: 46 · 2017: 54 · 2016: 56 · 2015: 50 · 2014: 60 · 2013: 64 · 2012: 57
- FWCI
- 40.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Nuclear Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Eli Lilly and Company
- Pfizer
- Vanderbilt University
- National Institutes of Health
- Avid Radiopharmaceuticals
- National Institute on Alcohol Abuse and Alcoholism (R01AA012839, AA012839)
- National Institute on Aging (K08AG029157, P50AG005146)
- National Institute of Mental Health (R01MH078175, MH 078175)
- National Institute on Drug Abuse (K24DA000412)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- Alzheimer's disease, amyloid-beta deposition, 18F-florbetapir, positron emission tomography, radioligands, amyloid imaging, distribution volume ratio, standardized uptake value ratio, dynamic PET, tracer metabolism, brain amyloid imaging, late-life cognitive impairment, cerebellum
- MeSH terms
- Aged, Alzheimer Disease, Amyloid, Aniline Compounds, Brain, Ethylene Glycols, Female, Fluorine Radioisotopes, Humans, Male, Radiometry, Whole-Body Irradiation, Case-Control Studies, Positron-Emission Tomography, Drug-Related Side Effects and Adverse Reactions
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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