The Experts below are selected from a list of 990 Experts worldwide ranked by ideXlab platform

Abhinay D Joshi - One of the best experts on this subject based on the ideXlab platform.

  • Florbetapir F 18 amyloid pet and 36 month cognitive decline a prospective multicenter study
    Molecular Psychiatry, 2014
    Co-Authors: P M Doraiswamy, Reisa A Sperling, K Johnson, Eric M Reiman, Terence Z Wong, Marwan N Sabbagh, Carl H Sadowsky, Adam S Fleisher, Alana Carpenter, Abhinay D Joshi
    Abstract:

    Florbetapir F 18 amyloid PET and 36-month cognitive decline:a prospective multicenter study

  • using positron emission tomography and Florbetapir F 18 to image cortical amyloid in patients with mild cognitive impairment or dementia due to alzheimer disease
    JAMA Neurology, 2011
    Co-Authors: Adam S Fleisher, Abhinay D Joshi, Christopher M Clark, Mark A Mintun, Kewei Chen, Xiaofen Liu, Auttawut Roontiva, Pradeep Thiyyagura, Napatkamon Ayutyanont, Michael J Pontecorvo
    Abstract:

    Objectives To characterize quantitative Florbetapir F 18 (hereaFter reFerred to as simply Florbetapir) positron emission tomographic (PET) measurements oF Fibrillar β-amyloid (Aβ) burden in a large clinical cohort oF participants with probable Alzheimer disease (AD) or mild cognitive impairment (MCI) and older healthy controls (OHCs). Design Cerebral–to–whole-cerebellar Florbetapir standard uptake value ratios (SUVRs) were computed. Mean cortical SUVRs were compared. A threshold oF SUVRs greater than or equal to 1.17 was used to reFlect pathological levels oF amyloid associated with AD based on separate antemortem PET and postmortem neuropathology data From 19 end-oF-liFe patients. Similarly, a threshold oF SUVRs greater than 1.08 was used to signiFy the presence oF any identiFiable Aβ because this was the upper limit From a separate set oF 46 individuals 18 to 40 years oF age who did not carry apolipoprotein E (APOE) e4. Setting Multiple research imaging centers. Participants A total oF 68 participants with probable AD, 60 participants with MCI, and 82 OHCs who were 55 years oF age or older. Main Outcome Measure Florbetapir-PET activity. Results All oF the participants (ie, those with probable AD or MCI and those who were OHCs) diFFered signiFicantly in mean (SD) cortical Florbetapir SUVRs (1.39 [0.24], 1.17 [0.27], and 1.05 [0.16], respectively; P  −7 ), in percentage meeting levels oF amyloid associated with AD by SUVR criteria (80.9%, 40.0%, and 20.7%, respectively; P  −7 ), and in percentage meeting SUVR criteria For the presence oF any identiFiable Aβ (85.3%, 46.6%, and 28.1%, respectively; P  −7 ). Among OHCs, the percentage oF Florbetapir positivity increased linearly by age decile (P = .05). For the 54 OHCs with available APOE genotypes, APOE e4 carriers had a higher mean (SD) cortical SUVR than did noncarriers (1.14 [0.2] vs 1.03 [0.16]; P = .048). Conclusions The Findings oF our analysis conFirm the ability oF Florbetapir-PET SUVRs to characterize amyloid levels in clinically probable AD, MCI, and OHC groups using continuous and binary measures oF Fibrillar Aβ burden. It introduces criteria to determine whether an image is associated with an intermediate-to-high likelihood oF pathologic AD or with having any identiFiable cortical amyloid level above that seen in low-risk young controls.

  • Florbetapir F 18 a histopathologically validated beta amyloid positron emission tomography imaging agent
    Seminars in Nuclear Medicine, 2011
    Co-Authors: John Listerjames, Abhinay D Joshi, Zhiping Zhuang, Geoff Golding, Seok Rye Choi, Christopher M Clark, Michael J Pontecorvo, Mark A Mintun, Tyler E Benedum
    Abstract:

    Florbetapir F-18 is a molecular imaging agent combining high aFFinity For β-amyloid, pharmacokinetic properties that allow positron emission tomography (PET) imaging within a convenient time aFter dose administration, and the wide availability oF the radionuclide Fluorine-18. Florbetapir F-18 is prepared by nucleophilic radioFluorination in approximately 60 minutes with a decay-corrected yield oF 20%-40% and with a speciFic activity typically exceeding 100 Ci/mmol. The Florbetapir F-18 dissociation constant (K d ) For binding to β-amyloid in brain tissue From Alzheimer's disease (AD) patients was 3.7 ± 0.3 nmol/L, and the maximum binding capacity (B max ) was 8800 ± 1600 Fmol/mg protein. Autoradiography studies have shown that Florbetapir F-18 selectively binds to β-amyloid aggregates in AD patient brain tissue, and the binding intensity is correlated with the density oF β-amyloid quantiFied by standard neuropathologic techniques. Studies in animals revealed no saFety concerns and rapid and transient normal brain uptake (6.8% injected dose/g at 2 minutes and 1.9% injected dose/g at 60 minutes in the mouse). Florbetapir F-18 has been well-tolerated in studies oF more than 2000 human subjects. Biodistribution studies in humans revealed predominantly hepatobiliary excretion. The whole body eFFective dose was 7 mSv From a dose oF 370 MBq. The pharmacokinetic oF Florbetapir F-18 make it possible to obtain a PET image with a brieF (10 minutes) acquisition time within a convenient time window oF 30-90 minutes aFter dose administration. Clinical studies have demonstrated a clear correlation between in vivo PET imaging with Florbetapir F-18 and postmortem histopathologic quantitation oF β-amyloid in the brain.

  • Florbetapir F 18 a histopathologically validated beta amyloid positron emission tomography imaging agent
    Seminars in Nuclear Medicine, 2011
    Co-Authors: John Listerjames, Abhinay D Joshi, Zhiping Zhuang, Geoff Golding, Seok Rye Choi, Christopher M Clark, Michael J Pontecorvo, Mark A Mintun, Wei Zhang, Tyler E Benedum
    Abstract:

    Florbetapir F-18 is a molecular imaging agent combining high aFFinity For β-amyloid, pharmacokinetic properties that allow positron emission tomography (PET) imaging within a convenient time aFter dose administration, and the wide availability oF the radionuclide Fluorine-18. Florbetapir F-18 is prepared by nucleophilic radioFluorination in approximately 60 minutes with a decay-corrected yield oF 20%-40% and with a speciFic activity typically exceeding 100 Ci/mmol. The Florbetapir F-18 dissociation constant (K d ) For binding to β-amyloid in brain tissue From Alzheimer's disease (AD) patients was 3.7 ± 0.3 nmol/L, and the maximum binding capacity (B max ) was 8800 ± 1600 Fmol/mg protein. Autoradiography studies have shown that Florbetapir F-18 selectively binds to β-amyloid aggregates in AD patient brain tissue, and the binding intensity is correlated with the density oF β-amyloid quantiFied by standard neuropathologic techniques. Studies in animals revealed no saFety concerns and rapid and transient normal brain uptake (6.8% injected dose/g at 2 minutes and 1.9% injected dose/g at 60 minutes in the mouse). Florbetapir F-18 has been well-tolerated in studies oF more than 2000 human subjects. Biodistribution studies in humans revealed predominantly hepatobiliary excretion. The whole body eFFective dose was 7 mSv From a dose oF 370 MBq. The pharmacokinetic oF Florbetapir F-18 make it possible to obtain a PET image with a brieF (10 minutes) acquisition time within a convenient time window oF 30-90 minutes aFter dose administration. Clinical studies have demonstrated a clear correlation between in vivo PET imaging with Florbetapir F-18 and postmortem histopathologic quantitation oF β-amyloid in the brain.

Michael J Pontecorvo - One of the best experts on this subject based on the ideXlab platform.

  • using positron emission tomography and Florbetapir F 18 to image cortical amyloid in patients with mild cognitive impairment or dementia due to alzheimer disease
    JAMA Neurology, 2011
    Co-Authors: Adam S Fleisher, Abhinay D Joshi, Christopher M Clark, Mark A Mintun, Kewei Chen, Xiaofen Liu, Auttawut Roontiva, Pradeep Thiyyagura, Napatkamon Ayutyanont, Michael J Pontecorvo
    Abstract:

    Objectives To characterize quantitative Florbetapir F 18 (hereaFter reFerred to as simply Florbetapir) positron emission tomographic (PET) measurements oF Fibrillar β-amyloid (Aβ) burden in a large clinical cohort oF participants with probable Alzheimer disease (AD) or mild cognitive impairment (MCI) and older healthy controls (OHCs). Design Cerebral–to–whole-cerebellar Florbetapir standard uptake value ratios (SUVRs) were computed. Mean cortical SUVRs were compared. A threshold oF SUVRs greater than or equal to 1.17 was used to reFlect pathological levels oF amyloid associated with AD based on separate antemortem PET and postmortem neuropathology data From 19 end-oF-liFe patients. Similarly, a threshold oF SUVRs greater than 1.08 was used to signiFy the presence oF any identiFiable Aβ because this was the upper limit From a separate set oF 46 individuals 18 to 40 years oF age who did not carry apolipoprotein E (APOE) e4. Setting Multiple research imaging centers. Participants A total oF 68 participants with probable AD, 60 participants with MCI, and 82 OHCs who were 55 years oF age or older. Main Outcome Measure Florbetapir-PET activity. Results All oF the participants (ie, those with probable AD or MCI and those who were OHCs) diFFered signiFicantly in mean (SD) cortical Florbetapir SUVRs (1.39 [0.24], 1.17 [0.27], and 1.05 [0.16], respectively; P  −7 ), in percentage meeting levels oF amyloid associated with AD by SUVR criteria (80.9%, 40.0%, and 20.7%, respectively; P  −7 ), and in percentage meeting SUVR criteria For the presence oF any identiFiable Aβ (85.3%, 46.6%, and 28.1%, respectively; P  −7 ). Among OHCs, the percentage oF Florbetapir positivity increased linearly by age decile (P = .05). For the 54 OHCs with available APOE genotypes, APOE e4 carriers had a higher mean (SD) cortical SUVR than did noncarriers (1.14 [0.2] vs 1.03 [0.16]; P = .048). Conclusions The Findings oF our analysis conFirm the ability oF Florbetapir-PET SUVRs to characterize amyloid levels in clinically probable AD, MCI, and OHC groups using continuous and binary measures oF Fibrillar Aβ burden. It introduces criteria to determine whether an image is associated with an intermediate-to-high likelihood oF pathologic AD or with having any identiFiable cortical amyloid level above that seen in low-risk young controls.

  • Florbetapir F 18 a histopathologically validated beta amyloid positron emission tomography imaging agent
    Seminars in Nuclear Medicine, 2011
    Co-Authors: John Listerjames, Abhinay D Joshi, Zhiping Zhuang, Geoff Golding, Seok Rye Choi, Christopher M Clark, Michael J Pontecorvo, Mark A Mintun, Wei Zhang, Tyler E Benedum
    Abstract:

    Florbetapir F-18 is a molecular imaging agent combining high aFFinity For β-amyloid, pharmacokinetic properties that allow positron emission tomography (PET) imaging within a convenient time aFter dose administration, and the wide availability oF the radionuclide Fluorine-18. Florbetapir F-18 is prepared by nucleophilic radioFluorination in approximately 60 minutes with a decay-corrected yield oF 20%-40% and with a speciFic activity typically exceeding 100 Ci/mmol. The Florbetapir F-18 dissociation constant (K d ) For binding to β-amyloid in brain tissue From Alzheimer's disease (AD) patients was 3.7 ± 0.3 nmol/L, and the maximum binding capacity (B max ) was 8800 ± 1600 Fmol/mg protein. Autoradiography studies have shown that Florbetapir F-18 selectively binds to β-amyloid aggregates in AD patient brain tissue, and the binding intensity is correlated with the density oF β-amyloid quantiFied by standard neuropathologic techniques. Studies in animals revealed no saFety concerns and rapid and transient normal brain uptake (6.8% injected dose/g at 2 minutes and 1.9% injected dose/g at 60 minutes in the mouse). Florbetapir F-18 has been well-tolerated in studies oF more than 2000 human subjects. Biodistribution studies in humans revealed predominantly hepatobiliary excretion. The whole body eFFective dose was 7 mSv From a dose oF 370 MBq. The pharmacokinetic oF Florbetapir F-18 make it possible to obtain a PET image with a brieF (10 minutes) acquisition time within a convenient time window oF 30-90 minutes aFter dose administration. Clinical studies have demonstrated a clear correlation between in vivo PET imaging with Florbetapir F-18 and postmortem histopathologic quantitation oF β-amyloid in the brain.

  • Florbetapir F 18 a histopathologically validated beta amyloid positron emission tomography imaging agent
    Seminars in Nuclear Medicine, 2011
    Co-Authors: John Listerjames, Abhinay D Joshi, Zhiping Zhuang, Geoff Golding, Seok Rye Choi, Christopher M Clark, Michael J Pontecorvo, Mark A Mintun, Tyler E Benedum
    Abstract:

    Florbetapir F-18 is a molecular imaging agent combining high aFFinity For β-amyloid, pharmacokinetic properties that allow positron emission tomography (PET) imaging within a convenient time aFter dose administration, and the wide availability oF the radionuclide Fluorine-18. Florbetapir F-18 is prepared by nucleophilic radioFluorination in approximately 60 minutes with a decay-corrected yield oF 20%-40% and with a speciFic activity typically exceeding 100 Ci/mmol. The Florbetapir F-18 dissociation constant (K d ) For binding to β-amyloid in brain tissue From Alzheimer's disease (AD) patients was 3.7 ± 0.3 nmol/L, and the maximum binding capacity (B max ) was 8800 ± 1600 Fmol/mg protein. Autoradiography studies have shown that Florbetapir F-18 selectively binds to β-amyloid aggregates in AD patient brain tissue, and the binding intensity is correlated with the density oF β-amyloid quantiFied by standard neuropathologic techniques. Studies in animals revealed no saFety concerns and rapid and transient normal brain uptake (6.8% injected dose/g at 2 minutes and 1.9% injected dose/g at 60 minutes in the mouse). Florbetapir F-18 has been well-tolerated in studies oF more than 2000 human subjects. Biodistribution studies in humans revealed predominantly hepatobiliary excretion. The whole body eFFective dose was 7 mSv From a dose oF 370 MBq. The pharmacokinetic oF Florbetapir F-18 make it possible to obtain a PET image with a brieF (10 minutes) acquisition time within a convenient time window oF 30-90 minutes aFter dose administration. Clinical studies have demonstrated a clear correlation between in vivo PET imaging with Florbetapir F-18 and postmortem histopathologic quantitation oF β-amyloid in the brain.

  • use oF Florbetapir pet For imaging β amyloid pathology
    JAMA, 2011
    Co-Authors: Christopher M Clark, Barry J Bedell, Alan Carpenter, Michael J Pontecorvo, Warren B Bilker, Franz Hefti, Julie A Schneider, Thomas G Beach, Mark A Mintun, Matthew Flitter
    Abstract:

    Context The ability to identiFy and quantiFy brain β-amyloid could increase the accuracy oF a clinical diagnosis oF Alzheimer disease. Objective To determine iF Florbetapir F 18 positron emission tomographic (PET) imaging perFormed during liFe accurately predicts the presence oF β-amyloid in the brain at autopsy. Design, Setting, and Participants Prospective clinical evaluation conducted February 2009 through March 2010 oF Florbetapir-PET imaging perFormed on 35 patients From hospice, long-term care, and community health care Facilities near the end oF their lives (6 patients to establish the protocol and 29 to validate) compared with immunohistochemistry and silver stain measures oF brain β-amyloid aFter their death used as the reFerence standard. PET images were also obtained in 74 young individuals (18-50 years) presumed Free oF brain amyloid to better understand the Frequency oF a False-positive interpretation oF a Florbetapir-PET image. Main Outcome Measures Correlation oF Florbetapir-PET image interpretation (based on the median oF 3 nuclear medicine physicians' ratings) and semiautomated quantiFication oF cortical retention with postmortem β-amyloid burden, neuritic amyloid plaque density, and neuropathological diagnosis oF Alzheimer disease in the First 35 participants autopsied (out oF 152 individuals enrolled in the PET pathological correlation study). Results Florbetapir-PET imaging was perFormed a mean oF 99 days (range, 1-377 days) beFore death For the 29 individuals in the primary analysis cohort. FiFteen oF the 29 individuals (51.7%) met pathological criteria For Alzheimer disease. Both visual interpretation oF the Florbetapir-PET images and mean quantitative estimates oF cortical uptake were correlated with presence and quantity oF β-amyloid pathology at autopsy as measured by immunohistochemistry (BonFerroni ρ, 0.78 [95% conFidence interval, 0.58-0.89]; P Conclusions Florbetapir-PET imaging was correlated with the presence and density oF β-amyloid. These data provide evidence that a molecular imaging procedure can identiFy β-amyloid pathology in the brains oF individuals during liFe. Additional studies are required to understand the appropriate use oF Florbetapir-PET imaging in the clinical diagnosis oF Alzheimer disease and For the prediction oF progression to dementia.

Adam S Fleisher - One of the best experts on this subject based on the ideXlab platform.

  • Florbetapir F 18 amyloid pet and 36 month cognitive decline a prospective multicenter study
    Molecular Psychiatry, 2014
    Co-Authors: P M Doraiswamy, Reisa A Sperling, K Johnson, Eric M Reiman, Terence Z Wong, Marwan N Sabbagh, Carl H Sadowsky, Adam S Fleisher, Alana Carpenter, Abhinay D Joshi
    Abstract:

    Florbetapir F 18 amyloid PET and 36-month cognitive decline:a prospective multicenter study

  • amyloid deposition detected with Florbetapir F 18 18F av 45 is related to lower episodic memory perFormance in clinically normal older individuals
    Neurobiology of Aging, 2013
    Co-Authors: Reisa A Sperling, Alan Carpenter, Eric M Reiman, Marwan N Sabbagh, Carl H Sadowsky, Adam S Fleisher, Murali P Doraiswamy, Keith A Johnson, Mat D Davis
    Abstract:

    Abstract The objective oF this study was to evaluate the relationship oF amyloid burden, as assessed by Florbetapir F 18 (18F-AV-45) amyloid positron emission tomography, and cognition in healthy older control (HC) subjects. Seventy-eight HC subjects were assessed with a brieF cognitive test battery and positron emission tomography (PET) imaging with 18F-AV-45. A standard uptake value ratio was computed For mean data From 6 cortical regions using a whole cerebellum reFerence region. Scans were also visually rated as amyloid positive or amyloid negative by 3 readers. Higher standard uptake value ratio correlated with lower immediate memory (r = −0.33; p = 0.003) and delayed recall scores (r = −0.25; p = 0.027). PerFormance on immediate recall was also lower in the visually rated amyloid positive compared with amyloid negative HC (p = 0.04), with a similar trend observed in delayed recall (p = 0.06). These Findings support the hypothesis that higher amyloid burden is associated with lower memory perFormance among clinically normal older subjects. Longitudinal Follow-up is ongoing to determine whether 18F-AV-45 may also predict subsequent cognitive decline.

  • amyloid β assessed by Florbetapir F 18 pet and 18 month cognitive decline a multicenter study
    Neurology, 2012
    Co-Authors: Murali P Doraiswamy, Reisa A Sperling, Eric M Reiman, Marwan N Sabbagh, Carl H Sadowsky, Edward R Coleman, Keith A Johnson, Mat D Davis, Michael Grundman, Adam S Fleisher
    Abstract:

    Objectives: Florbetapir F 18 PET can image amyloid-β (Aβ) aggregates in the brains oF living subjects. We prospectively evaluated the prognostic utility oF detecting Aβ pathology using Florbetapir PET in subjects at risk For progressive cognitive decline. Methods: A total oF 151 subjects who previously participated in a multicenter Florbetapir PET imaging study were recruited For longitudinal assessment. Subjects included 51 with recently diagnosed mild cognitive impairment (MCI), 69 cognitively normal controls (CN), and 31 with clinically diagnosed Alzheimer disease dementia (AD). PET images were visually scored as positive (Aβ+) or negative (Aβ−) For pathologic levels oF β-amyloid aggregation, blind to diagnostic classiFication. Cerebral to cerebellar standardized uptake value ratios (SUVr) were determined From the baseline PET images. Subjects were Followed For 18 months to evaluate changes in cognition and diagnostic status. Analysis oF covariance and correlation analyses were conducted to evaluate the association between baseline PET amyloid status and subsequent cognitive decline. Results: In both MCI and CN, baseline Aβ+ scans were associated with greater clinical worsening on the Alzheimer’s Disease Assessment Scale–Cognitive subscale (ADAS-Cog ( p p p p p p p Conclusions: Florbetapir PET may help identiFy individuals at increased risk For progressive cognitive decline.

  • using positron emission tomography and Florbetapir F 18 to image cortical amyloid in patients with mild cognitive impairment or dementia due to alzheimer disease
    JAMA Neurology, 2011
    Co-Authors: Adam S Fleisher, Abhinay D Joshi, Christopher M Clark, Mark A Mintun, Kewei Chen, Xiaofen Liu, Auttawut Roontiva, Pradeep Thiyyagura, Napatkamon Ayutyanont, Michael J Pontecorvo
    Abstract:

    Objectives To characterize quantitative Florbetapir F 18 (hereaFter reFerred to as simply Florbetapir) positron emission tomographic (PET) measurements oF Fibrillar β-amyloid (Aβ) burden in a large clinical cohort oF participants with probable Alzheimer disease (AD) or mild cognitive impairment (MCI) and older healthy controls (OHCs). Design Cerebral–to–whole-cerebellar Florbetapir standard uptake value ratios (SUVRs) were computed. Mean cortical SUVRs were compared. A threshold oF SUVRs greater than or equal to 1.17 was used to reFlect pathological levels oF amyloid associated with AD based on separate antemortem PET and postmortem neuropathology data From 19 end-oF-liFe patients. Similarly, a threshold oF SUVRs greater than 1.08 was used to signiFy the presence oF any identiFiable Aβ because this was the upper limit From a separate set oF 46 individuals 18 to 40 years oF age who did not carry apolipoprotein E (APOE) e4. Setting Multiple research imaging centers. Participants A total oF 68 participants with probable AD, 60 participants with MCI, and 82 OHCs who were 55 years oF age or older. Main Outcome Measure Florbetapir-PET activity. Results All oF the participants (ie, those with probable AD or MCI and those who were OHCs) diFFered signiFicantly in mean (SD) cortical Florbetapir SUVRs (1.39 [0.24], 1.17 [0.27], and 1.05 [0.16], respectively; P  −7 ), in percentage meeting levels oF amyloid associated with AD by SUVR criteria (80.9%, 40.0%, and 20.7%, respectively; P  −7 ), and in percentage meeting SUVR criteria For the presence oF any identiFiable Aβ (85.3%, 46.6%, and 28.1%, respectively; P  −7 ). Among OHCs, the percentage oF Florbetapir positivity increased linearly by age decile (P = .05). For the 54 OHCs with available APOE genotypes, APOE e4 carriers had a higher mean (SD) cortical SUVR than did noncarriers (1.14 [0.2] vs 1.03 [0.16]; P = .048). Conclusions The Findings oF our analysis conFirm the ability oF Florbetapir-PET SUVRs to characterize amyloid levels in clinically probable AD, MCI, and OHC groups using continuous and binary measures oF Fibrillar Aβ burden. It introduces criteria to determine whether an image is associated with an intermediate-to-high likelihood oF pathologic AD or with having any identiFiable cortical amyloid level above that seen in low-risk young controls.

Tyler E Benedum - One of the best experts on this subject based on the ideXlab platform.

  • Florbetapir F 18 a histopathologically validated beta amyloid positron emission tomography imaging agent
    Seminars in Nuclear Medicine, 2011
    Co-Authors: John Listerjames, Abhinay D Joshi, Zhiping Zhuang, Geoff Golding, Seok Rye Choi, Christopher M Clark, Michael J Pontecorvo, Mark A Mintun, Tyler E Benedum
    Abstract:

    Florbetapir F-18 is a molecular imaging agent combining high aFFinity For β-amyloid, pharmacokinetic properties that allow positron emission tomography (PET) imaging within a convenient time aFter dose administration, and the wide availability oF the radionuclide Fluorine-18. Florbetapir F-18 is prepared by nucleophilic radioFluorination in approximately 60 minutes with a decay-corrected yield oF 20%-40% and with a speciFic activity typically exceeding 100 Ci/mmol. The Florbetapir F-18 dissociation constant (K d ) For binding to β-amyloid in brain tissue From Alzheimer's disease (AD) patients was 3.7 ± 0.3 nmol/L, and the maximum binding capacity (B max ) was 8800 ± 1600 Fmol/mg protein. Autoradiography studies have shown that Florbetapir F-18 selectively binds to β-amyloid aggregates in AD patient brain tissue, and the binding intensity is correlated with the density oF β-amyloid quantiFied by standard neuropathologic techniques. Studies in animals revealed no saFety concerns and rapid and transient normal brain uptake (6.8% injected dose/g at 2 minutes and 1.9% injected dose/g at 60 minutes in the mouse). Florbetapir F-18 has been well-tolerated in studies oF more than 2000 human subjects. Biodistribution studies in humans revealed predominantly hepatobiliary excretion. The whole body eFFective dose was 7 mSv From a dose oF 370 MBq. The pharmacokinetic oF Florbetapir F-18 make it possible to obtain a PET image with a brieF (10 minutes) acquisition time within a convenient time window oF 30-90 minutes aFter dose administration. Clinical studies have demonstrated a clear correlation between in vivo PET imaging with Florbetapir F-18 and postmortem histopathologic quantitation oF β-amyloid in the brain.

  • Florbetapir F 18 a histopathologically validated beta amyloid positron emission tomography imaging agent
    Seminars in Nuclear Medicine, 2011
    Co-Authors: John Listerjames, Abhinay D Joshi, Zhiping Zhuang, Geoff Golding, Seok Rye Choi, Christopher M Clark, Michael J Pontecorvo, Mark A Mintun, Wei Zhang, Tyler E Benedum
    Abstract:

    Florbetapir F-18 is a molecular imaging agent combining high aFFinity For β-amyloid, pharmacokinetic properties that allow positron emission tomography (PET) imaging within a convenient time aFter dose administration, and the wide availability oF the radionuclide Fluorine-18. Florbetapir F-18 is prepared by nucleophilic radioFluorination in approximately 60 minutes with a decay-corrected yield oF 20%-40% and with a speciFic activity typically exceeding 100 Ci/mmol. The Florbetapir F-18 dissociation constant (K d ) For binding to β-amyloid in brain tissue From Alzheimer's disease (AD) patients was 3.7 ± 0.3 nmol/L, and the maximum binding capacity (B max ) was 8800 ± 1600 Fmol/mg protein. Autoradiography studies have shown that Florbetapir F-18 selectively binds to β-amyloid aggregates in AD patient brain tissue, and the binding intensity is correlated with the density oF β-amyloid quantiFied by standard neuropathologic techniques. Studies in animals revealed no saFety concerns and rapid and transient normal brain uptake (6.8% injected dose/g at 2 minutes and 1.9% injected dose/g at 60 minutes in the mouse). Florbetapir F-18 has been well-tolerated in studies oF more than 2000 human subjects. Biodistribution studies in humans revealed predominantly hepatobiliary excretion. The whole body eFFective dose was 7 mSv From a dose oF 370 MBq. The pharmacokinetic oF Florbetapir F-18 make it possible to obtain a PET image with a brieF (10 minutes) acquisition time within a convenient time window oF 30-90 minutes aFter dose administration. Clinical studies have demonstrated a clear correlation between in vivo PET imaging with Florbetapir F-18 and postmortem histopathologic quantitation oF β-amyloid in the brain.

Mark A Mintun - One of the best experts on this subject based on the ideXlab platform.

  • using positron emission tomography and Florbetapir F 18 to image cortical amyloid in patients with mild cognitive impairment or dementia due to alzheimer disease
    JAMA Neurology, 2011
    Co-Authors: Adam S Fleisher, Abhinay D Joshi, Christopher M Clark, Mark A Mintun, Kewei Chen, Xiaofen Liu, Auttawut Roontiva, Pradeep Thiyyagura, Napatkamon Ayutyanont, Michael J Pontecorvo
    Abstract:

    Objectives To characterize quantitative Florbetapir F 18 (hereaFter reFerred to as simply Florbetapir) positron emission tomographic (PET) measurements oF Fibrillar β-amyloid (Aβ) burden in a large clinical cohort oF participants with probable Alzheimer disease (AD) or mild cognitive impairment (MCI) and older healthy controls (OHCs). Design Cerebral–to–whole-cerebellar Florbetapir standard uptake value ratios (SUVRs) were computed. Mean cortical SUVRs were compared. A threshold oF SUVRs greater than or equal to 1.17 was used to reFlect pathological levels oF amyloid associated with AD based on separate antemortem PET and postmortem neuropathology data From 19 end-oF-liFe patients. Similarly, a threshold oF SUVRs greater than 1.08 was used to signiFy the presence oF any identiFiable Aβ because this was the upper limit From a separate set oF 46 individuals 18 to 40 years oF age who did not carry apolipoprotein E (APOE) e4. Setting Multiple research imaging centers. Participants A total oF 68 participants with probable AD, 60 participants with MCI, and 82 OHCs who were 55 years oF age or older. Main Outcome Measure Florbetapir-PET activity. Results All oF the participants (ie, those with probable AD or MCI and those who were OHCs) diFFered signiFicantly in mean (SD) cortical Florbetapir SUVRs (1.39 [0.24], 1.17 [0.27], and 1.05 [0.16], respectively; P  −7 ), in percentage meeting levels oF amyloid associated with AD by SUVR criteria (80.9%, 40.0%, and 20.7%, respectively; P  −7 ), and in percentage meeting SUVR criteria For the presence oF any identiFiable Aβ (85.3%, 46.6%, and 28.1%, respectively; P  −7 ). Among OHCs, the percentage oF Florbetapir positivity increased linearly by age decile (P = .05). For the 54 OHCs with available APOE genotypes, APOE e4 carriers had a higher mean (SD) cortical SUVR than did noncarriers (1.14 [0.2] vs 1.03 [0.16]; P = .048). Conclusions The Findings oF our analysis conFirm the ability oF Florbetapir-PET SUVRs to characterize amyloid levels in clinically probable AD, MCI, and OHC groups using continuous and binary measures oF Fibrillar Aβ burden. It introduces criteria to determine whether an image is associated with an intermediate-to-high likelihood oF pathologic AD or with having any identiFiable cortical amyloid level above that seen in low-risk young controls.

  • Florbetapir F 18 a histopathologically validated beta amyloid positron emission tomography imaging agent
    Seminars in Nuclear Medicine, 2011
    Co-Authors: John Listerjames, Abhinay D Joshi, Zhiping Zhuang, Geoff Golding, Seok Rye Choi, Christopher M Clark, Michael J Pontecorvo, Mark A Mintun, Wei Zhang, Tyler E Benedum
    Abstract:

    Florbetapir F-18 is a molecular imaging agent combining high aFFinity For β-amyloid, pharmacokinetic properties that allow positron emission tomography (PET) imaging within a convenient time aFter dose administration, and the wide availability oF the radionuclide Fluorine-18. Florbetapir F-18 is prepared by nucleophilic radioFluorination in approximately 60 minutes with a decay-corrected yield oF 20%-40% and with a speciFic activity typically exceeding 100 Ci/mmol. The Florbetapir F-18 dissociation constant (K d ) For binding to β-amyloid in brain tissue From Alzheimer's disease (AD) patients was 3.7 ± 0.3 nmol/L, and the maximum binding capacity (B max ) was 8800 ± 1600 Fmol/mg protein. Autoradiography studies have shown that Florbetapir F-18 selectively binds to β-amyloid aggregates in AD patient brain tissue, and the binding intensity is correlated with the density oF β-amyloid quantiFied by standard neuropathologic techniques. Studies in animals revealed no saFety concerns and rapid and transient normal brain uptake (6.8% injected dose/g at 2 minutes and 1.9% injected dose/g at 60 minutes in the mouse). Florbetapir F-18 has been well-tolerated in studies oF more than 2000 human subjects. Biodistribution studies in humans revealed predominantly hepatobiliary excretion. The whole body eFFective dose was 7 mSv From a dose oF 370 MBq. The pharmacokinetic oF Florbetapir F-18 make it possible to obtain a PET image with a brieF (10 minutes) acquisition time within a convenient time window oF 30-90 minutes aFter dose administration. Clinical studies have demonstrated a clear correlation between in vivo PET imaging with Florbetapir F-18 and postmortem histopathologic quantitation oF β-amyloid in the brain.

  • Florbetapir F 18 a histopathologically validated beta amyloid positron emission tomography imaging agent
    Seminars in Nuclear Medicine, 2011
    Co-Authors: John Listerjames, Abhinay D Joshi, Zhiping Zhuang, Geoff Golding, Seok Rye Choi, Christopher M Clark, Michael J Pontecorvo, Mark A Mintun, Tyler E Benedum
    Abstract:

    Florbetapir F-18 is a molecular imaging agent combining high aFFinity For β-amyloid, pharmacokinetic properties that allow positron emission tomography (PET) imaging within a convenient time aFter dose administration, and the wide availability oF the radionuclide Fluorine-18. Florbetapir F-18 is prepared by nucleophilic radioFluorination in approximately 60 minutes with a decay-corrected yield oF 20%-40% and with a speciFic activity typically exceeding 100 Ci/mmol. The Florbetapir F-18 dissociation constant (K d ) For binding to β-amyloid in brain tissue From Alzheimer's disease (AD) patients was 3.7 ± 0.3 nmol/L, and the maximum binding capacity (B max ) was 8800 ± 1600 Fmol/mg protein. Autoradiography studies have shown that Florbetapir F-18 selectively binds to β-amyloid aggregates in AD patient brain tissue, and the binding intensity is correlated with the density oF β-amyloid quantiFied by standard neuropathologic techniques. Studies in animals revealed no saFety concerns and rapid and transient normal brain uptake (6.8% injected dose/g at 2 minutes and 1.9% injected dose/g at 60 minutes in the mouse). Florbetapir F-18 has been well-tolerated in studies oF more than 2000 human subjects. Biodistribution studies in humans revealed predominantly hepatobiliary excretion. The whole body eFFective dose was 7 mSv From a dose oF 370 MBq. The pharmacokinetic oF Florbetapir F-18 make it possible to obtain a PET image with a brieF (10 minutes) acquisition time within a convenient time window oF 30-90 minutes aFter dose administration. Clinical studies have demonstrated a clear correlation between in vivo PET imaging with Florbetapir F-18 and postmortem histopathologic quantitation oF β-amyloid in the brain.

  • use oF Florbetapir pet For imaging β amyloid pathology
    JAMA, 2011
    Co-Authors: Christopher M Clark, Barry J Bedell, Alan Carpenter, Michael J Pontecorvo, Warren B Bilker, Franz Hefti, Julie A Schneider, Thomas G Beach, Mark A Mintun, Matthew Flitter
    Abstract:

    Context The ability to identiFy and quantiFy brain β-amyloid could increase the accuracy oF a clinical diagnosis oF Alzheimer disease. Objective To determine iF Florbetapir F 18 positron emission tomographic (PET) imaging perFormed during liFe accurately predicts the presence oF β-amyloid in the brain at autopsy. Design, Setting, and Participants Prospective clinical evaluation conducted February 2009 through March 2010 oF Florbetapir-PET imaging perFormed on 35 patients From hospice, long-term care, and community health care Facilities near the end oF their lives (6 patients to establish the protocol and 29 to validate) compared with immunohistochemistry and silver stain measures oF brain β-amyloid aFter their death used as the reFerence standard. PET images were also obtained in 74 young individuals (18-50 years) presumed Free oF brain amyloid to better understand the Frequency oF a False-positive interpretation oF a Florbetapir-PET image. Main Outcome Measures Correlation oF Florbetapir-PET image interpretation (based on the median oF 3 nuclear medicine physicians' ratings) and semiautomated quantiFication oF cortical retention with postmortem β-amyloid burden, neuritic amyloid plaque density, and neuropathological diagnosis oF Alzheimer disease in the First 35 participants autopsied (out oF 152 individuals enrolled in the PET pathological correlation study). Results Florbetapir-PET imaging was perFormed a mean oF 99 days (range, 1-377 days) beFore death For the 29 individuals in the primary analysis cohort. FiFteen oF the 29 individuals (51.7%) met pathological criteria For Alzheimer disease. Both visual interpretation oF the Florbetapir-PET images and mean quantitative estimates oF cortical uptake were correlated with presence and quantity oF β-amyloid pathology at autopsy as measured by immunohistochemistry (BonFerroni ρ, 0.78 [95% conFidence interval, 0.58-0.89]; P Conclusions Florbetapir-PET imaging was correlated with the presence and density oF β-amyloid. These data provide evidence that a molecular imaging procedure can identiFy β-amyloid pathology in the brains oF individuals during liFe. Additional studies are required to understand the appropriate use oF Florbetapir-PET imaging in the clinical diagnosis oF Alzheimer disease and For the prediction oF progression to dementia.