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Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging 9/2016

30.03.2016 | Original Article

Early [18F]florbetaben and [11C]PiB PET images are a surrogate biomarker of neuronal injury in Alzheimer’s disease

verfasst von: Solveig Tiepolt, Swen Hesse, Marianne Patt, Julia Luthardt, Matthias L. Schroeter, Karl-Titus Hoffmann, David Weise, Hermann-Josef Gertz, Osama Sabri, Henryk Barthel

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 9/2016

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Abstract

Purpose

[18F]FDG is a commonly used neuronal injury biomarker for early and differential diagnosis of dementia. Typically, the blood supply to the brain is closely coupled to glucose consumption. Early uptake of the Aβ tracer [11C]PiB on PET images is mainly determined by cerebral blood flow and shows a high correlation with [18F]FDG uptake. Uptake data for 18F-labelled Aβ PET tracers are, however, scarce. We investigated the value of early PET images using the novel Aβ tracer [18F]FBB in the diagnosis of Alzhimers disease (AD).

Methods

This retrospective analysis included 22 patients with MCI or dementia who underwent dual time-point PET imaging with either [11C]PiB (11 patients) or [18F]FBB (11 patients) in routine clinical practice. Images were acquired 1 – 9 min after administration of both tracers and 40 – 70 min and 90 – 110 min after administration of [11C]PiB and [18F]FBB, respectively. The patients also underwent [18F]FDG brain PET imaging. PET data were analysed visually and semiquantitatively. Associations between early Aβ tracer uptake and dementia as well as brain atrophy were investigated.

Results

Regional visual scores of early Aβ tracer and [18F]FDG PET images were significantly correlated (Spearman’s ρ = 0.780, P < 0.001). Global brain visual analysis revealed identical results between early Aβ tracer and [18F]FDG PET images. In a VOI-based analysis, the early Aβ tracer data correlated significantly with the [18F]FDG data (r = 0.779, P < 0.001), but there were no differences between [18F]FBB and [11C]PiB. Cortical SUVRs in regions typically affected in AD on early Aβ tracer and [18F]FDG PET images were correlated with MMSE scores (ρ = 0.458, P = 0.032, and ρ = 0.456, P = 0.033, respectively). A voxel-wise group-based search for areas with relatively higher tracer uptake on early Aβ tracer PET images compared with [18F]FDG PET images revealed a small cluster in the midbrain/pons; no significant clusters were found for the opposite comparison.

Conclusion

Early [18F]FBB and [11C]PiB PET brain images are similar to [18F]FDG PET images in AD patients, and these tracers could potentially be used as biomarkers in place of [18F]FDG. Thus, Aβ tracer PET imaging has the potential to provide biomarker information on AD pathology and neuronal injury. The potential of this approach for supporting the diagnosis of AD needs to be confirmed in prospective studies in larger cohorts.
Literatur
1.
Zurück zum Zitat McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR, Kawas CH, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):263–9.CrossRefPubMedPubMedCentral McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR, Kawas CH, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):263–9.CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Dubois B, Feldman HH, Jacova C, Hampel H, Molinuevo JL, Blennow K, et al. Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria. Lancet Neurol. 2014;13(6):614–29.CrossRefPubMed Dubois B, Feldman HH, Jacova C, Hampel H, Molinuevo JL, Blennow K, et al. Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria. Lancet Neurol. 2014;13(6):614–29.CrossRefPubMed
3.
Zurück zum Zitat Tiepolt S, Barthel H, Butzke D, Hesse S, Patt M, Gertz H, et al. Influence of scan duration on the accuracy of β-amyloid PET with florbetaben in patients with Alzheimer’s disease and healthy volunteers. Eur J Nucl Med Mol Imaging. 2013;40(2):238–44.CrossRefPubMed Tiepolt S, Barthel H, Butzke D, Hesse S, Patt M, Gertz H, et al. Influence of scan duration on the accuracy of β-amyloid PET with florbetaben in patients with Alzheimer’s disease and healthy volunteers. Eur J Nucl Med Mol Imaging. 2013;40(2):238–44.CrossRefPubMed
4.
Zurück zum Zitat Barthel H, Seibyl J, Sabri O. The role of positron emission tomography imaging in understanding Alzheimer’s disease [ENG]. Expert review of neurotherapeutics. Expert Rev Neurother. 2015;15(4):395–406.CrossRefPubMed Barthel H, Seibyl J, Sabri O. The role of positron emission tomography imaging in understanding Alzheimer’s disease [ENG]. Expert review of neurotherapeutics. Expert Rev Neurother. 2015;15(4):395–406.CrossRefPubMed
7.
Zurück zum Zitat Meyer PT, Hellwig S, Amtage F, Rottenburger C, Sahm U, Reuland P, et al. Dual-biomarker imaging of regional cerebral amyloid load and neuronal activity in dementia with PET and 11C-labeled Pittsburgh compound B. J Nucl Med. 2011;52(3):393–400.CrossRefPubMed Meyer PT, Hellwig S, Amtage F, Rottenburger C, Sahm U, Reuland P, et al. Dual-biomarker imaging of regional cerebral amyloid load and neuronal activity in dementia with PET and 11C-labeled Pittsburgh compound B. J Nucl Med. 2011;52(3):393–400.CrossRefPubMed
8.
Zurück zum Zitat Becker GA, Ichise M, Barthel H, Luthardt J, Patt M, Seese A, et al. PET quantification of 18F-florbetaben binding to β-amyloid deposits in human brains. J Nucl Med. 2013;54(5):723–31.CrossRefPubMed Becker GA, Ichise M, Barthel H, Luthardt J, Patt M, Seese A, et al. PET quantification of 18F-florbetaben binding to β-amyloid deposits in human brains. J Nucl Med. 2013;54(5):723–31.CrossRefPubMed
9.
Zurück zum Zitat Rostomian AH, Madison C, Rabinovici GD, Jagust WJ. Early 11C-PIB frames and 18F-FDG PET measures are comparable: a study validated in a cohort of AD and FTLD patients. J Nucl Med. 2011;52(2):173–9.PubMedPubMedCentral Rostomian AH, Madison C, Rabinovici GD, Jagust WJ. Early 11C-PIB frames and 18F-FDG PET measures are comparable: a study validated in a cohort of AD and FTLD patients. J Nucl Med. 2011;52(2):173–9.PubMedPubMedCentral
10.
Zurück zum Zitat Forsberg A, Engler H, Blomquist G, Långström B, Nordberg A. The use of PIB-PET as a dual pathological and functional biomarker in AD. Biochim Biophys Acta. 2012;1822(3):380–5.CrossRefPubMed Forsberg A, Engler H, Blomquist G, Långström B, Nordberg A. The use of PIB-PET as a dual pathological and functional biomarker in AD. Biochim Biophys Acta. 2012;1822(3):380–5.CrossRefPubMed
11.
Zurück zum Zitat Hsiao I, Huang C, Hsieh C, Hsu W, Wey S, Yen T, et al. Correlation of early-phase 18F-florbetapir (AV-45/Amyvid) PET images to FDG images: preliminary studies. Eur J Nucl Med Mol Imaging. 2012;39(4):613–20.CrossRefPubMed Hsiao I, Huang C, Hsieh C, Hsu W, Wey S, Yen T, et al. Correlation of early-phase 18F-florbetapir (AV-45/Amyvid) PET images to FDG images: preliminary studies. Eur J Nucl Med Mol Imaging. 2012;39(4):613–20.CrossRefPubMed
12.
Zurück zum Zitat McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology. 1984;34(7):939–44.CrossRefPubMed McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology. 1984;34(7):939–44.CrossRefPubMed
13.
Zurück zum Zitat Werner P, Barthel H, Drzezga A, Sabri O. Current status and future role of brain PET/MRI in clinical and research settings. Eur J Nucl Med Mol Imaging. 2015;42(3):512–26.CrossRefPubMed Werner P, Barthel H, Drzezga A, Sabri O. Current status and future role of brain PET/MRI in clinical and research settings. Eur J Nucl Med Mol Imaging. 2015;42(3):512–26.CrossRefPubMed
14.
Zurück zum Zitat Barthel H, Gertz H, Dresel S, Peters O, Bartenstein P, Buerger K, et al. Cerebral amyloid-β PET with florbetaben (18F) in patients with Alzheimer’s disease and healthy controls: a multicentre phase 2 diagnostic study. Lancet Neurol. 2011;10(5):424–35.CrossRefPubMed Barthel H, Gertz H, Dresel S, Peters O, Bartenstein P, Buerger K, et al. Cerebral amyloid-β PET with florbetaben (18F) in patients with Alzheimer’s disease and healthy controls: a multicentre phase 2 diagnostic study. Lancet Neurol. 2011;10(5):424–35.CrossRefPubMed
15.
Zurück zum Zitat Price JC, Klunk WE, Lopresti BJ, Lu X, Hoge JA, Ziolko SK, et al. Kinetic modeling of amyloid binding in humans using PET imaging and Pittsburgh Compound-B. J Cereb Blood Flow Metab. 2005;25(11):1528–47.CrossRefPubMed Price JC, Klunk WE, Lopresti BJ, Lu X, Hoge JA, Ziolko SK, et al. Kinetic modeling of amyloid binding in humans using PET imaging and Pittsburgh Compound-B. J Cereb Blood Flow Metab. 2005;25(11):1528–47.CrossRefPubMed
16.
Zurück zum Zitat Suotunen T, Hirvonen J, Immonen-Räihä P, Aalto S, Lisinen I, Arponen E, et al. Visual assessment of [(11)C]PIB PET in patients with cognitive impairment. Eur J Nucl Med Mol Imaging. 2010;37(6):1141–7.CrossRefPubMed Suotunen T, Hirvonen J, Immonen-Räihä P, Aalto S, Lisinen I, Arponen E, et al. Visual assessment of [(11)C]PIB PET in patients with cognitive impairment. Eur J Nucl Med Mol Imaging. 2010;37(6):1141–7.CrossRefPubMed
17.
Zurück zum Zitat Barthel H, Luthardt J, Becker G, Patt M, Hammerstein E, Hartwig K, et al. Individualized quantification of brain β-amyloid burden: results of a proof of mechanism phase 0 florbetaben PET trial in patients with Alzheimer’s disease and healthy controls. Eur J Nucl Med Mol Imaging. 2011;38(9):1702–14.CrossRefPubMed Barthel H, Luthardt J, Becker G, Patt M, Hammerstein E, Hartwig K, et al. Individualized quantification of brain β-amyloid burden: results of a proof of mechanism phase 0 florbetaben PET trial in patients with Alzheimer’s disease and healthy controls. Eur J Nucl Med Mol Imaging. 2011;38(9):1702–14.CrossRefPubMed
18.
Zurück zum Zitat Sabri O, Sabbagh MN, Seibyl J, Barthel H, Akatsu H, Ouchi Y, et al. Florbetaben PET imaging to detect amyloid beta plaques in Alzheimer disease: phase 3 study. Alzheimers Dement. 2015;11(8):964–74. doi:10.1016/j.jalz.2015.02.004. Sabri O, Sabbagh MN, Seibyl J, Barthel H, Akatsu H, Ouchi Y, et al. Florbetaben PET imaging to detect amyloid beta plaques in Alzheimer disease: phase 3 study. Alzheimers Dement. 2015;11(8):964–74. doi:10.​1016/​j.​jalz.​2015.​02.​004.
21.
Zurück zum Zitat Villemagne VL, Mulligan RS, Pejoska S, Ong K, Jones G, O’Keefe G, et al. Comparison of 11C-PiB and 18F-florbetaben for Aβ imaging in ageing and Alzheimer’s disease. Eur J Nucl Med Mol Imaging. 2012;39(6):983–9.CrossRefPubMed Villemagne VL, Mulligan RS, Pejoska S, Ong K, Jones G, O’Keefe G, et al. Comparison of 11C-PiB and 18F-florbetaben for Aβ imaging in ageing and Alzheimer’s disease. Eur J Nucl Med Mol Imaging. 2012;39(6):983–9.CrossRefPubMed
22.
Zurück zum Zitat Scheltens P, Leys D, Barkhof F, Huglo D, Weinstein HC, Vermersch P, et al. Atrophy of medial temporal lobes on MRI in “probable” Alzheimer’s disease and normal ageing: diagnostic value and neuropsychological correlates. J Neurol Neurosurg Psychiatry. 1992;55(10):967–72.CrossRefPubMedPubMedCentral Scheltens P, Leys D, Barkhof F, Huglo D, Weinstein HC, Vermersch P, et al. Atrophy of medial temporal lobes on MRI in “probable” Alzheimer’s disease and normal ageing: diagnostic value and neuropsychological correlates. J Neurol Neurosurg Psychiatry. 1992;55(10):967–72.CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Blomquist G, Engler H, Nordberg A, Ringheim A, Wall A, Forsberg A, et al. Unidirectional Influx and net accumulation of PIB. Open Neuroimag J. 2008;2:114–25.CrossRefPubMedPubMedCentral Blomquist G, Engler H, Nordberg A, Ringheim A, Wall A, Forsberg A, et al. Unidirectional Influx and net accumulation of PIB. Open Neuroimag J. 2008;2:114–25.CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Arlt S, Brassen S, Jahn H, Wilke F, Eichenlaub M, Apostolova I, et al. Association between FDG uptake, CSF biomarkers and cognitive performance in patients with probable Alzheimer’s disease. Eur J Nucl Med Mol Imaging. 2009;36(7):1090–100.CrossRefPubMed Arlt S, Brassen S, Jahn H, Wilke F, Eichenlaub M, Apostolova I, et al. Association between FDG uptake, CSF biomarkers and cognitive performance in patients with probable Alzheimer’s disease. Eur J Nucl Med Mol Imaging. 2009;36(7):1090–100.CrossRefPubMed
26.
Zurück zum Zitat Kadir A, Almkvist O, Forsberg A, Wall A, Engler H, Långström B, et al. Dynamic changes in PET amyloid and FDG imaging at different stages of Alzheimer’s disease. Neurobiol Aging. 2012;33(1):98.e1–14. Kadir A, Almkvist O, Forsberg A, Wall A, Engler H, Långström B, et al. Dynamic changes in PET amyloid and FDG imaging at different stages of Alzheimer’s disease. Neurobiol Aging. 2012;33(1):98.e1–14.
27.
Zurück zum Zitat Johnson KA, Minoshima S, Bohnen NI, Donohoe KJ, Foster NL, Herscovitch P, et al. Appropriate use criteria for amyloid PET: a report of the Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer's Association. J Nucl Med. 2013;54:476–90.CrossRefPubMed Johnson KA, Minoshima S, Bohnen NI, Donohoe KJ, Foster NL, Herscovitch P, et al. Appropriate use criteria for amyloid PET: a report of the Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer's Association. J Nucl Med. 2013;54:476–90.CrossRefPubMed
28.
Zurück zum Zitat Booij J, Arbizu J, Darcourt J, Hesse S, Nobili F, Payoux P, et al. Appropriate use criteria for amyloid PET imaging cannot replace guidelines: on behalf of the European Association of Nuclear Medicine. Eur J Nucl Med Mol Imaging. 2013;40(7):1122–5.CrossRefPubMed Booij J, Arbizu J, Darcourt J, Hesse S, Nobili F, Payoux P, et al. Appropriate use criteria for amyloid PET imaging cannot replace guidelines: on behalf of the European Association of Nuclear Medicine. Eur J Nucl Med Mol Imaging. 2013;40(7):1122–5.CrossRefPubMed
Metadaten
Titel
Early [18F]florbetaben and [11C]PiB PET images are a surrogate biomarker of neuronal injury in Alzheimer’s disease
verfasst von
Solveig Tiepolt
Swen Hesse
Marianne Patt
Julia Luthardt
Matthias L. Schroeter
Karl-Titus Hoffmann
David Weise
Hermann-Josef Gertz
Osama Sabri
Henryk Barthel
Publikationsdatum
30.03.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 9/2016
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-016-3353-1

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