Comparison of 11C-PiB and 18F-florbetaben for Aβ imaging in ageing and Alzheimer’s disease

  • Victor L. Villemagne
  • Rachel S. Mulligan
  • Svetlana Pejoska
  • Kevin Ong
  • Gareth Jones
  • Graeme O’Keefe
  • J. Gordon Chan
  • Kenneth Young
  • Henri Tochon-Danguy
  • Colin L. Masters
  • Christopher C. Rowe
Original Article

Abstract

Purpose

Amyloid imaging with 18F-labelled radiotracers will allow widespread use of this technique, facilitating research, diagnosis and therapeutic development for Alzheimer’s disease (AD). The purpose of this analysis was to compare data on cortical Aβ deposition in subjects who had undergone both 11C-PiB (PiB) and 18F-florbetaben (FBB) PET imaging.

Methods

We identified ten healthy elderly controls (HC) and ten patients with AD who had undergone PET imaging after intravenous injection of 370 MBq of PiB and 300 MBq of FBB under separate research protocols. PiB and FBB images were coregistered so that placement of regions of interest was identical on both scans and standard uptake value ratios (SUVR) using the cerebellar cortex as reference region were calculated between 40 and 70 min and between 90 and 110 min after injection for PiB and FBB, respectively.

Results

Significantly higher SUVR values (p < 0.0001) in most cortical areas were observed in AD patients when compared with HC with both radiotracers. Global SUVR values in AD patients were on average 75% higher than in HC with PiB and 56% higher with FBB. There was an excellent linear correlation between PiB and FBB global SUVR values (r = 0.97, p < 0.0001) with similar effect sizes for distinguishing AD from HC subjects for both radiotracers (Cohen’s d 3.3 for PiB and 3.0 for FBB).

Conclusion

FBB, while having a narrower dynamic range than PiB, clearly distinguished HC from AD patients, with a comparable effect size. FBB seems a suitable 18F radiotracer for imaging AD pathology in vivo.

Keywords

Alzheimer’s disease Amyloid imaging Aβ Positron emission tomography 

References

  1. 1.
    Villemagne VL, Fodero-Tavoletti MT, Pike KE, Cappai R, Masters CL, Rowe CC. The ART of loss: abeta imaging in the evaluation of Alzheimer's disease and other dementias. Mol Neurobiol. 2008;38(1):1–15.PubMedCrossRefGoogle Scholar
  2. 2.
    Rowe CC, Ng S, Ackermann U, Gong SJ, Pike K, Savage G, et al. Imaging beta-amyloid burden in aging and dementia. Neurology. 2007;68(20):1718–25.PubMedCrossRefGoogle Scholar
  3. 3.
    Klunk WE, Engler H, Nordberg A, Wang Y, Blomqvist G, Holt DP, et al. Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B. Ann Neurol. 2004;55(3):306–19.PubMedCrossRefGoogle Scholar
  4. 4.
    Rabinovici GD, Furst AJ, O'Neil JP, Racine CA, Mormino EC, Baker SL, et al. 11C-PIB PET imaging in Alzheimer disease and frontotemporal lobar degeneration. Neurology. 2007;68(15):1205–12.PubMedCrossRefGoogle Scholar
  5. 5.
    Fagan AM, Mintun MA, Mach RH, Lee SY, Dence CS, Shah AR, et al. Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Abeta(42) in humans. Ann Neurol. 2006;59(3):512–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Bacskai BJ, Frosch MP, Freeman SH, Raymond SB, Augustinack JC, Johnson KA, et al. Molecular imaging with Pittsburgh Compound B confirmed at autopsy: a case report. Arch Neurol. 2007;64(3):431–4.PubMedCrossRefGoogle Scholar
  7. 7.
    Leinonen V, Alafuzoff I, Aalto S, Suotunen T, Savolainen S, Nagren K, et al. Assessment of beta-amyloid in a frontal cortical brain biopsy specimen and by positron emission tomography with carbon 11-labeled Pittsburgh Compound B. Arch Neurol. 2008;65(10):1304–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Ikonomovic MD, Klunk WE, Abrahamson EE, Mathis CA, Price JC, Tsopelas ND, et al. Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease. Brain. 2008;131(Pt 6):1630–45.PubMedCrossRefGoogle Scholar
  9. 9.
    Chetelat G, Villemagne VL, Bourgeat P, Pike KE, Jones G, Ames D, et al. Relationship between atrophy and beta-amyloid deposition in Alzheimer disease. Ann Neurol. 2010;67(3):317–24.PubMedGoogle Scholar
  10. 10.
    Pike KE, Savage G, Villemagne VL, Ng S, Moss SA, Maruff P, et al. Beta-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer's disease. Brain. 2007;130(Pt 11):2837–44.PubMedCrossRefGoogle Scholar
  11. 11.
    Resnick SM, Sojkova J, Zhou Y, An Y, Ye W, Holt DP, et al. Longitudinal cognitive decline is associated with fibrillar amyloid-beta measured by [11C]PiB. Neurology. 2010;74(10):807–15.PubMedCrossRefGoogle Scholar
  12. 12.
    Villemagne VL, Pike KE, Chetelat G, Ellis KA, Mulligan RS, Bourgeat P, et al. Longitudinal assessment of Abeta and cognition in aging and Alzheimer disease. Ann Neurol. 2011;69(1):181–92.PubMedCrossRefGoogle Scholar
  13. 13.
    McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack Jr 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. Alzheim Dement. 2011;7(3):263–9.CrossRefGoogle Scholar
  14. 14.
    Rowe CC, Villemagne VL. Brain amyloid imaging. J Nucl Med. 2011;52(11):1733–40.PubMedCrossRefGoogle Scholar
  15. 15.
    Villemagne VL, Rowe CC. Amyloid ligands for dementia. PET Clin. 2010;5:33–53.CrossRefGoogle Scholar
  16. 16.
    Rowe CC, Ackerman U, Browne W, Mulligan R, Pike KL, O'Keefe G, et al. Imaging of amyloid beta in Alzheimer's disease with (18)F-BAY94-9172, a novel PET tracer: proof of mechanism. Lancet Neurol. 2008;7(2):129–35.PubMedCrossRefGoogle Scholar
  17. 17.
    Wong DF, Rosenberg PB, Zhou Y, Kumar A, Raymont V, Ravert HT, et al. In vivo imaging of amyloid deposition in Alzheimer disease using the radioligand 18F-AV-45 (flobetapir F 18). J Nucl Med. 2010;51(6):913–20.PubMedCrossRefGoogle Scholar
  18. 18.
    Vandenberghe R, Van Laere K, Ivanoiu A, Salmon E, Bastin C, Triau E, et al. 18F-flutemetamol amyloid imaging in Alzheimer disease and mild cognitive impairment: a phase 2 trial. Ann Neurol. 2010;68(3):319–29.PubMedCrossRefGoogle Scholar
  19. 19.
    Jureus A, Swahn BM, Sandell J, Jeppsson F, Johnson AE, Johnstrom P, et al. Characterization of AZD4694, a novel fluorinated Abeta plaque neuroimaging PET radioligand. J Neurochem. 2010;114(3):784–94.PubMedCrossRefGoogle Scholar
  20. 20.
    Clark CM, Schneider JA, Bedell BJ, Beach TG, Bilker WB, Mintun MA, et al. Use of florbetapir-PET for imaging beta-amyloid pathology. JAMA. 2011;305(3):275–83.PubMedCrossRefGoogle Scholar
  21. 21.
    Barthel H, Gertz HJ, Dresel S, Peters O, Bartenstein P, Buerger K, et al. Cerebral amyloid-beta PET with florbetaben ((18)F) in patients with Alzheimer's disease and healthy controls: a multicentre phase 2 diagnostic study. Lancet Neurol. 2011;10(5):424–35.PubMedCrossRefGoogle Scholar
  22. 22.
    Ong K, Villemagne VL, Lamngon N, Holl G, Reininger C, Putz B, et al. Assessment of Aβ deposition in mild cognitive impairment with 18F-florbetaben. Alzheim Dement. 2010;6(4):S26.CrossRefGoogle Scholar
  23. 23.
    Braak H, Braak E. Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiol Aging. 1997;18(4):351–7.PubMedCrossRefGoogle Scholar
  24. 24.
    Villemagne VL, Ong K, Mulligan RS, Holl G, Pejoska S, Jones G, et al. Amyloid imaging with 18F-florbetaben in Alzheimer disease and other dementias. J Nucl Med. 2011;52(8):1210–7.PubMedCrossRefGoogle Scholar
  25. 25.
    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;34:939–44.PubMedGoogle Scholar
  26. 26.
    Good CD, Johnsrude IS, Ashburner J, Henson RN, Friston KJ, Frackowiak RS. A voxel-based morphometric study of ageing in 465 normal adult human brains. Neuroimage. 2001;14(1 Pt 1):21–36.PubMedCrossRefGoogle Scholar
  27. 27.
    Ng S, Villemagne VL, Berlangieri S, Lee ST, Cherk M, Gong SJ, et al. Visual assessment versus quantitative assessment of 11C-PIB PET and 18F-FDG PET for detection of Alzheimer's disease. J Nucl Med. 2007;48(4):547–52.PubMedCrossRefGoogle Scholar
  28. 28.
    Aizenstein HJ, Nebes RD, Saxton JA, Price JC, Mathis CA, Tsopelas ND, et al. Frequent amyloid deposition without significant cognitive impairment among the elderly. Arch Neurol. 2008;65(11):1509–17.PubMedCrossRefGoogle Scholar
  29. 29.
    Villemagne VL, Pike KE, Darby D, Maruff P, Savage G, Ng S, et al. Abeta deposits in older non-demented individuals with cognitive decline are indicative of preclinical Alzheimer's disease. Neuropsychologia. 2008;46(6):1688–97.PubMedCrossRefGoogle Scholar
  30. 30.
    Bennett DA, Schneider JA, Arvanitakis Z, Kelly JF, Aggarwal NT, Shah RC, et al. Neuropathology of older persons without cognitive impairment from two community-based studies. Neurology. 2006;66(12):1837–44.PubMedCrossRefGoogle Scholar
  31. 31.
    Price JL, Morris JC. Tangles and plaques in nondemented aging and "preclinical" Alzheimer's disease. Ann Neurol. 1999;45(3):358–68.PubMedCrossRefGoogle Scholar
  32. 32.
    Jack Jr CR, Lowe VJ, Weigand SD, Wiste HJ, Senjem ML, Knopman DS, et al. Serial PIB and MRI in normal, mild cognitive impairment and Alzheimer's disease: implications for sequence of pathological events in Alzheimer's disease. Brain. 2009;132(Pt 5):1355–65.PubMedCrossRefGoogle Scholar
  33. 33.
    Sojkova J, Zhou Y, An Y, Kraut MA, Ferrucci L, Wong DF, et al. Longitudinal patterns of beta-amyloid deposition in nondemented older adults. Arch Neurol. 2011;68(5):644–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Victor L. Villemagne
    • 1
    • 2
    • 3
  • Rachel S. Mulligan
    • 1
  • Svetlana Pejoska
    • 1
  • Kevin Ong
    • 1
  • Gareth Jones
    • 1
  • Graeme O’Keefe
    • 1
  • J. Gordon Chan
    • 1
  • Kenneth Young
    • 1
  • Henri Tochon-Danguy
    • 1
  • Colin L. Masters
    • 3
  • Christopher C. Rowe
    • 1
    • 2
  1. 1.Department of Nuclear Medicine and Centre for PETAustin HealthHeidelbergAustralia
  2. 2.Department of MedicineUniversity of MelbourneParkvilleAustralia
  3. 3.The Mental Health Research Institute of VictoriaParkvilleAustralia

Personalised recommendations