Skip to main content

Advertisement

SpringerLink
Log in

Amyloid PET imaging in Alzheimer’s disease: a comparison of three radiotracers

  • Original Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

The increasing use of amyloid PET in Alzheimer’s disease research and clinical trials has motivated efforts to standardize methodology. We compared retention of the 11C radiotracer Pittsburgh Compound B (PiB) and that of two 18F amyloid radiotracers (florbetapir and flutemetamol) using two study populations. We also examined the feasibility of converting between tracer-specific measures, using PiB as the common link between the two 18F tracers.

Methods

One group of 40 subjects underwent PiB and flutemetamol imaging sessions and a separate group of 32 subjects underwent PiB and florbetapir imaging sessions. We compared cortical and white matter retention for each 18F tracer relative to that of PiB, as well as retention in several reference regions and image analysis methods. Correlations between tracer pairs were used to convert tracer-specific threshold values for amyloid positivity between tracers.

Results

Cortical retention for each pair of tracers was strongly correlated regardless of reference region (PiB–flutemetamol, ρ = 0.84–0.99; PiB–florbetapir, ρ = 0.83–0.97) and analysis method (ρ = 0.90–0.99). Compared to PiB, flutemetamol had higher white matter retention, while florbetapir had lower cortical retention. Two previously established independent thresholds for amyloid positivity were highly consistent when values were converted between tracer pairs.

Conclusion

Despite differing white and grey matter retention characteristics, cortical retention for each 18F tracer was highly correlated with that of PiB, enabling conversion of thresholds across tracer measurement scales with a high level of internal consistency. Standardization of analysis methods and measurement scales may facilitate the comparison of amyloid PET data obtained using different tracers.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Rowe CC, Ackerman U, Browne W, Mulligan R, Pike KL, O'Keefe G, et al. Imaging of amyloid beta in Alzheimer's disease with 18F-BAY94-9172, a novel PET tracer: proof of mechanism. Lancet Neurol. 2008;7(2):129–35. doi:10.1016/S1474-4422(08)70001-2.

    Article  CAS  PubMed  Google Scholar 

  2. 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. doi:10.1002/ana.22068.

    Article  PubMed  Google Scholar 

  3. Villemagne VL, Mulligan RS, Pejoska S, Ong K, Jones G, O'Keefe G, et al. Comparison of 11C-PiB and 18F-florbetaben for Abeta imaging in ageing and Alzheimer's disease. Eur J Nucl Med Mol Imaging. 2012;39(6):983–9. doi:10.1007/s00259-012-2088-x.

    Article  CAS  PubMed  Google Scholar 

  4. Wolk DA, Zhang Z, Boudhar S, Clark CM, Pontecorvo MJ, Arnold SE. Amyloid imaging in Alzheimer's disease: comparison of florbetapir and Pittsburgh compound-B positron emission tomography. J Neurol Neurosurg Psychiatry. 2012;83(9):923–6. doi:10.1136/jnnp-2012-302548.

    Article  PubMed  Google Scholar 

  5. Cselenyi Z, Jonhagen ME, Forsberg A, Halldin C, Julin P, Schou M, et al. Clinical validation of 18F-AZD4694, an amyloid-beta-specific PET radioligand. J Nucl Med. 2012;53(3):415–24. doi:10.2967/jnumed.111.094029.

    Article  CAS  PubMed  Google Scholar 

  6. Landau SM, Breault C, Joshi AD, Pontecorvo M, Mathis CA, Jagust WJ, et al. Amyloid-beta imaging with Pittsburgh compound B and florbetapir: comparing radiotracers and quantification methods. J Nucl Med. 2013;54(1):70–7. doi:10.2967/jnumed.112.109009.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. 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 (florbetapir [corrected] F 18). J Nucl Med. 2010;51(6):913–20. doi:10.2967/jnumed.109.069088.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Forsberg A, Engler H, Almkvist O, Blomquist G, Hagman G, Wall A, et al. PET imaging of amyloid deposition in patients with mild cognitive impairment. Neurobiol Aging. 2008;29(10):1456–65. doi:10.1016/j.neurobiolaging.2007.03.029.

    Article  CAS  PubMed  Google Scholar 

  9. 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. doi:10.1212/01.wnl.0000261919.22630.ea.

    Article  CAS  PubMed  Google Scholar 

  10. Fodero-Tavoletti MT, Rowe CC, McLean CA, Leone L, Li QX, Masters CL, et al. Characterization of PiB binding to white matter in Alzheimer disease and other dementias. J Nucl Med. 2009;50(2):198–204. doi:10.2967/jnumed.108.057984.

    Article  PubMed  Google Scholar 

  11. Nelissen N, Van Laere K, Thurfjell L, Owenius R, Vandenbulcke M, Koole M, et al. Phase 1 study of the Pittsburgh compound B derivative 18F-flutemetamol in healthy volunteers and patients with probable Alzheimer disease. J Nucl Med. 2009;50(8):1251–9. doi:10.2967/jnumed.109.063305.

    Article  CAS  PubMed  Google Scholar 

  12. Thomas BA, Erlandsson K, Modat M, Thurfjell L, Vandenberghe R, Ourselin S, et al. The importance of appropriate partial volume correction for PET quantification in Alzheimer's disease. Eur J Nucl Med Mol Imaging. 2011;38(6):1104–19. doi:10.1007/s00259-011-1745-9.

    Article  PubMed  Google Scholar 

  13. 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. doi:10.1002/ana.20009.

    Article  CAS  PubMed  Google Scholar 

  14. Landau SM, Marks SM, Mormino EC, Rabinovici GD, Oh H, O'Neil JP, et al. Association of lifetime cognitive engagement and low beta-amyloid deposition. Arch Neurol. 2012;69(5):623–9. doi:10.1001/archneurol.2011.2748.

    Article  PubMed Central  PubMed  Google Scholar 

  15. Mormino EC, Kluth JT, Madison CM, Rabinovici GD, Baker SL, Miller BL, et al. Episodic memory loss is related to hippocampal-mediated beta-amyloid deposition in elderly subjects. Brain. 2009;132(Pt 5):1310–23. doi:10.1093/brain/awn320.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Lundqvist R, Lilja J, Thomas BA, Lotjonen J, Villemagne VL, Rowe CC, et al. Implementation and validation of an adaptive template registration method for 18F-flutemetamol imaging data. J Nucl Med. 2013;54(8):1472–8. doi:10.2967/jnumed.112.115006.

    Article  CAS  PubMed  Google Scholar 

  17. Jagust WJ, Landau SM, Shaw LM, Trojanowski JQ, Koeppe RA, Reiman EM, et al. Relationships between biomarkers in aging and dementia. Neurology. 2009;73(15):1193–9. doi:10.1212/WNL.0b013e3181bc010c.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Joshi AD, Pontecorvo MJ, Clark CM, Carpenter AP, Jennings DL, Sadowsky CH, et al. Performance characteristics of amyloid PET with florbetapir F 18 in patients with alzheimer's disease and cognitively normal subjects. J Nucl Med. 2012;53(3):378–84. doi:10.2967/jnumed.111.090340.

    Article  CAS  PubMed  Google Scholar 

  19. Clark CM, Pontecorvo MJ, Beach TG, Bedell BJ, Coleman RE, Doraiswamy PM, et al. Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-beta plaques: a prospective cohort study. Lancet Neurol. 2012;11(8):669–78. doi:10.1016/S1474-4422(12)70142-4.

    Article  CAS  PubMed  Google Scholar 

  20. Landau SM, Mintun M, Joshi A, Koeppe RA, Petersen RC, Aisen P, et al. Amyloid deposition, hypometabolism, and longitudinal cognitive decline. Ann Neurol. 2012;72(4):578–86. doi:10.1002/ana.23650.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Tolboom N, Yaqub M, Boellaard R, Luurtsema G, Windhorst AD, Scheltens P, et al. Test-retest variability of quantitative [11C]PIB studies in Alzheimer's disease. Eur J Nucl Med Mol Imaging. 2009;36(10):1629–38. doi:10.1007/s00259-009-1129-6.

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Robert Koeppe, Abhinay Joshi, and Cindee Madison for helpful discussions and assistance with image analysis.

B.T. acknowledges the support of GlaxoSmithKline (GSK) and also that UCL/UCLH receives a portion of its research funding from the UK Department of Health Biomedical Research Centre’s funding scheme.

Data collection and sharing for this project was funded by the ADNI (National Institutes of Health grant U01 AG024904). ADNI is funded by the National Institute on Aging, and the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott; Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Amorfix Life Sciences Ltd.; AstraZeneca; Bayer HealthCare; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research provides funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129 and K01 AG030514.

Conflicts of interest

S.M. Landau has previously consulted for Avid Radiopharmaceuticals, Inc., Janssen Alzheimer Immunotherapy, and Biogen Idec.

B.A. Thomas has performed research under a grant partially supported by GE Healthcare.

L. Thurfjell is an employee of GE Healthcare.

M. Schmidt is an employee of Janssen Research and Development.

R. Margolin is an employee of Janssen Alzheimer Immunotherapy R&D LLC.

M. Pontecorvo and M. Mintun are employees of Avid Radiopharmaceuticals, Inc.

W.J. Jagust collaborates with Avid Radiopharmaceuticals, Inc. through participation in the ADNI. He has previously consulted for GE Healthcare, Genentech, and Elan/Janssen Alzheimer Immunotherapy, and is currently a consultant to F. Hoffman-LaRoche and Synarc.

Author information

Authors and Affiliations

  1. Helen Wills Neuroscience Institute, University of California, Berkeley, 118 Barker Hall MC #3190, Berkeley, CA, 94720-3190, USA

    S. M. Landau & W. J. Jagust

  2. Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA

    S. M. Landau, S. L. Baker & W. J. Jagust

  3. Institute of Nuclear Medicine, University College London, London, UK

    B. A. Thomas

  4. GE Healthcare, Uppsala, Sweden

    L. Thurfjell

  5. Janssen Pharmaceutica, NV, Beerse, Belgium

    M. Schmidt

  6. Janssen Alzheimer Immunotherapy, South San Francisco, CA, USA

    R. Margolin

  7. Avid Radiopharmaceuticals, Inc., Philadelphia, PA, USA

    M. Mintun & M. Pontecorvo

Authors
  1. S. M. Landau
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. A. Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. Thurfjell
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Schmidt
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R. Margolin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. Mintun
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M. Pontecorvo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. S. L. Baker
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. W. J. Jagust
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

the Alzheimer’s Disease Neuroimaging Initiative

Corresponding author

Correspondence to S. M. Landau.

Additional information

Data used in the preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu/). As such, the ADNI investigators contributed to the design and implementation of ADNI and/or provided data, but did not participate in the analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/about/governance

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary table

(DOCX 64 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Landau, S.M., Thomas, B.A., Thurfjell, L. et al. Amyloid PET imaging in Alzheimer’s disease: a comparison of three radiotracers. Eur J Nucl Med Mol Imaging 41, 1398–1407 (2014). https://doi.org/10.1007/s00259-014-2753-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-014-2753-3

Keywords

Search

Navigation