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.
Similar content being viewed by others
References
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Rowe CC, Villemagne VL. Brain amyloid imaging. J Nucl Med. 2011;52(11):1733–40.
Villemagne VL, Rowe CC. Amyloid ligands for dementia. PET Clin. 2010;5:33–53.
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.
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.
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.
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.
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.
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.
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.
Braak H, Braak E. Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiol Aging. 1997;18(4):351–7.
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.
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.
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.
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.
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.
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.
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.
Price JL, Morris JC. Tangles and plaques in nondemented aging and "preclinical" Alzheimer's disease. Ann Neurol. 1999;45(3):358–68.
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.
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.
Acknowledgments
We thank Prof. Michael Woodward, Dr. John Merory, Dr. Peter Drysdale, Dr. Sylvia Gong, Ms. Fiona Lamb, Ms. Tanya Petts, Ms. Jessica Sagona, Mr. Ignatius Reilly and Mr. Jason Bradley, and the Brain Research Institute, for their assistance with this study.
This work was supported in part by grant 509166 from the National Health and Medical Research Council of Australia, the Austin Hospital Medical Research Foundation, and Neurosciences Victoria.
Conflicts of interest
Drs. Villemagne and Rowe are consultants for Bayer Healthcare AG.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Villemagne, V.L., Mulligan, R.S., Pejoska, S. et al. Comparison of 11C-PiB and 18F-florbetaben for Aβ imaging in ageing and Alzheimer’s disease. Eur J Nucl Med Mol Imaging 39, 983–989 (2012). https://doi.org/10.1007/s00259-012-2088-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00259-012-2088-x