Molecular imaging in the diagnosis of Alzheimer's disease: visual assessment of [11C]PIB and [18F]FDDNP PET images
- Nelleke Tolboom1,2,
- Wiesje M van der Flier2,3,
- Jolanda Boverhoff2,
- Maqsood Yaqub1,
- Mike P Wattjes4,
- Pieter G Raijmakers1,
- Frederik Barkhof4,
- Philip Scheltens2,
- Karl Herholz5,
- Adriaan A Lammertsma1,
- Bart N M van Berckel1
- 1Department of Nuclear Medicine & PET Research, VU University Medical Centre, Amsterdam, The Netherlands
- 2Department of Neurology and Alzheimer Centre, VU University Medical Centre, Amsterdam, The Netherlands
- 3Department of Epidemiology and Biostatistics, VU University Medical Centre, Amsterdam, The Netherlands
- 4Department of Radiology, VU University Medical Centre, Amsterdam, The Netherlands
- 5Wolfson Molecular Imaging Centre, The University of Manchester, Manchester, UK
- Correspondence to Mrs Nelleke Tolboom, Department of Neurology & Alzheimer Centre, VU University Medical Centre, PO Box 7057, Amsterdam, 1007 MB, The Netherlands;
- Received 13 September 2009
- Revised 17 December 2009
- Accepted 18 December 2009
- Published Online First 11 June 2010
Objective To evaluate visual assessment of [11C]PIB and [18F]FDDNP PET images as potential supportive diagnostic markers for Alzheimer's disease (AD).
Methods Twenty-one AD patients and 20 controls were included. Parametric [11C]PIB and [18F]FDDNP global binding potential (BPND) images were visually rated as ‘AD’ or ‘normal.’ Data were compared with ratings of [18F]FDG PET images and MRI-derived medial temporal lobe atrophy (MTA) scores. Inter-rater agreement and agreement with clinical diagnosis were assessed for all imaging modalities. In addition, cut-off values for quantitative global [11C]PIB and [18F]FDDNP BPND were determined. Visual ratings were compared with dichotomised quantitative values.
Results Agreement between readers was excellent for [11C]PIB, [18F]FDDNP and MTA (Cohen kappa κ≥0.85) and moderate for [18F]FDG (κ=0.56). The highest sensitivity was found for [11C]PIB and [18F]FDG (both 1.0). The highest specificity was found for MTA (0.90) and [11C]PIB (0.85). [18F]FDDNP had the lowest sensitivity and specificity (0.67 and 0.53, respectively). The cut-off for quantitative [11C]PIB BPND was 0.54 (sensitivity and specificity both 0.95) and for [18F]FDDNP BPND 0.07 (sensitivity 0.80, specificity 0.73). Agreement between quantitative analyses and visual ratings was excellent for [11C]PIB (κ=0.85) and fair for [18F]FDDNP (κ=0.40).
Conclusion Visual assessment of [11C]PIB images was straightforward and accurate, showing promise as a supportive diagnostic marker for AD. Moreover, [11C]PIB showed the best combination of sensitivity and specificity. Visual assessment of [18F]FDDNP images was insufficient. The quantitative analysis of [18F]FDDNP data showed a considerably higher diagnostic value than the visual analysis.
Funding This work was financially supported by the Internationale Stichting Alzheimer Onderzoek (ISAO, grant 05512), and the American Health Assistance Foundation (AHAF, grant A2005-026).
Competing interests PS serves/has served as Associate Editor of the Journal of Neurology, Neurosurgery & Psychiatry.
Ethics approval Ethics approval was provided by the Medical Ethics Review Committee of the VU University Medical Centre Amsterdam.
Provenance and peer review Not commissioned; externally peer reviewed.