Amyloid- Imaging with Pittsburgh Compound B and Florbetapir: Comparing Radiotracers and Quantification Methods

Helen Wills Neuroscience Institute, University of California, Berkeley, California.
Journal of Nuclear Medicine (Impact Factor: 6.16). 11/2012; 54(1). DOI: 10.2967/jnumed.112.109009
Source: PubMed


(11)C-Pittsburgh compound B ((11)C-PiB) and (18)F-florbetapir amyloid-β (Aβ) PET radioligands have had a substantial impact on Alzheimer disease research. Although there is evidence that both radioligands bind to fibrillar Aβ in the brain, direct comparisons in the same individuals have not been reported. Here, we evaluated PiB and florbetapir in a retrospective convenience sample of cognitively normal older controls, patients with mild cognitive impairment, and patients with Alzheimer disease from the Alzheimer's Disease Neuroimaging Initiative (ADNI).

From the ADNI database, 32 participants were identified who had undergone at least 1 PiB study and subsequently underwent a florbetapir study approximately 1.5 y after the last PiB study. Cortical PiB and florbetapir retention was quantified using several different methods to determine the effect of preprocessing factors (such as smoothing and reference region selection) and image processing pipelines.

There was a strong association between PiB and florbetapir cortical retention ratios (Spearman ρ = 0.86-0.95), and these were slightly lower than cortical retention ratios for consecutive PiB scans (Spearman ρ = 0.96-0.98) made approximately 1.1 y apart. Cortical retention ratios for Aβ-positive subjects tended to be higher for PiB than for florbetapir images, yielding slopes for linear regression of florbetapir against PiB of 0.59-0.64. Associations between consecutive PiB scans and between PiB and florbetapir scans remained strong, regardless of processing methods such as smoothing, spatial normalization to a PET template, and use of reference regions. The PiB-florbetapir association was used to interconvert cutoffs for Aβ positivity and negativity between the 2 radioligands, and these cutoffs were highly consistent in their assignment of Aβ status.

PiB and florbetapir retention ratios were strongly associated in the same individuals, and this relationship was consistent across several data analysis methods, despite scan-rescan intervals of more than a year. Cutoff thresholds for determining positive or negative Aβ status can be reliably transformed from PiB to florbetapir units or vice versa using a population scanned with both radioligands.

1 Follower
45 Reads
  • Source
    • "In a recent study, 11C-PiB and florbetapir PET were compared in a retrospective sample of cognitively normal older controls, patients with MCI, and patients with AD. 11C-PiB and florbetapir retention ratios were strongly associated in the same individuals, and the relationship was consistent across several data analysis methods, despite scan-rescan intervals of more than a year. The findings of this study indicate that cutoff thresholds for determining positive or negative amyloid-β status can be reliably transformed from PIB to florbetapir units or vice versa using a population scanned with both radiopharmaceuticals [71]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: PET based tools can improve the early diagnosis of Alzheimer's disease (AD) and differential diagnosis of dementia. The importance of identifying individuals at risk of developing dementia among people with subjective cognitive complaints or mild cognitive impairment has clinical, social, and therapeutic implications. Within the two major classes of AD biomarkers currently identified, that is, markers of pathology and neurodegeneration, amyloid- and FDG-PET imaging represent decisive tools for their measurement. As a consequence, the PET tools have been recognized to be of crucial value in the recent guidelines for the early diagnosis of AD and other dementia conditions. The references based recommendations, however, include large PET imaging literature based on visual methods that greatly reduces sensitivity and specificity and lacks a clear cut-off between normal and pathological findings. PET imaging can be assessed using parametric or voxel-wise analyses by comparing the subject's scan with a normative data set, significantly increasing the diagnostic accuracy. This paper is a survey of the relevant literature on FDG and amyloid-PET imaging aimed at providing the value of quantification for the early and differential diagnosis of AD. This allowed a meta-analysis and GRADE analysis revealing high values for PET imaging that might be useful in considering recommendations.
    03/2014; 2014(17):785039. DOI:10.1155/2014/785039
  • Source
    • "This could also partly explain the significant differences we found between route 1 and route 2 that were not found by Edison et al. [25]. In another recent study, Landau et al. investigated amyloid ligand uptake using PiB and AV-45 in a patients with mild cognitive impairment compared to healthy subjects [29]. They used similar methods to our routes 1 and 2 for cortical quantification, and found similar results between the two routes. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Florbetapir (AV-45) has been shown to be a reliable tool for assessing in vivo amyloid load in patients with Alzheimer's disease from the early stages. However, nonspecific white matter binding has been reported in healthy subjects as well as in patients with Alzheimer's disease. To avoid this issue, cortical quantification might increase the reliability of AV-45 PET analyses. In this study, we compared two quantification methods for AV-45 binding, a classical method relying on PET template registration (route 1), and a MRI-based method (route 2) for cortical quantification. We recruited 22 patients at the prodromal stage of Alzheimer's disease and 17 matched controls. AV-45 binding was assessed using both methods, and target-to-cerebellum mean global standard uptake values (SUVr) were obtained for each of them, together with SUVr in specific regions of interest. Quantification using the two routes was compared between the clinical groups (intragroup comparison), and between groups for each route (intergroup comparison). Discriminant analysis was performed. In the intragroup comparison, differences in uptake values were observed between route 1 and route 2 in both groups. In the intergroup comparison, AV-45 uptake was higher in patients than controls in all regions of interest using both methods, but the effect size of this difference was larger using route 2. In the discriminant analysis, route 2 showed a higher specificity (94.1 % versus 70.6 %), despite a lower sensitivity (77.3 % versus 86.4 %), and D-prime values were higher for route 2. These findings suggest that, although both quantification methods enabled patients at early stages of Alzheimer's disease to be well discriminated from controls, PET template-based quantification seems adequate for clinical use, while the MRI-based cortical quantification method led to greater intergroup differences and may be more suitable for use in current clinical research.
    European Journal of Nuclear Medicine 12/2013; 41(5). DOI:10.1007/s00259-013-2656-8 · 5.38 Impact Factor
  • Source
    • "The second is the uncertain choice of a region of reference of specific flow and no specific binding. The cerebellum is held to be little affected by amyloid deposition in AD, and the cerebellar gray matter often serves as reference region for measures of [ 11 C]PIB retention (Landau et al., 2013), but other regions have been considered as well, including whole cerebellum (Joshi et al., 2012), and the Pons (Klunk et al., 2007; Knight et al., 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Rapid clearance and disappearance of a tracer from the circulation challenges the determination of the tracer's binding potentials in brain (BP ND) by positron emission tomography (PET). This is the case for the analysis of the binding of radiolabeled [(11)C]Pittsburgh Compound B ([(11)C]PIB) to amyloid-β (Aβ) plaques in brain of patients with Alzheimer's disease (AD). To resolve the issue of rapid clearance from the circulation, we here introduce the flow-independent Washout Allometric Reference Method (WARM) for the analysis of washout and binding of [(11)C]PIB in two groups of human subjects, healthy aged control subjects (HC), and patients suffering from AD, and we compare the results to the outcome of two conventional analysis methods. We also use the rapid initial clearance to obtain a surrogate measure of the rate of cerebral blood flow (CBF), as well as a method of identifying a suitable reference region directly from the [(11)C]PIB signal. The difference of average absolute CBF values between the AD and HC groups was highly significant (P < 0.003). The CBF measures were not significantly different between the groups when normalized to cerebellar gray matter flow. Thus, when flow differences confound conventional measures of [(11)C]PIB binding, the separate estimates of CBF and BP ND provide additional information about possible AD. The results demonstrate the importance of data-driven estimation of CBF and BP ND, as well as reference region detection from the [(11)C]PIB signal. We conclude that the WARM method yields stable measures of BP ND with relative ease, using only integration for noise reduction and no model regression. The method accounts for relative flow differences in the brain tissue and yields a calibrated measure of absolute CBF directly from the [(11)C]PIB signal. Compared to conventional methods, WARM optimizes the Aβ plaque load discrimination between patients with AD and healthy controls (P = 0.009).
    Frontiers in Aging Neuroscience 11/2013; 5:45. DOI:10.3389/fnagi.2013.00045 · 4.00 Impact Factor
Show more