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

ArticleinJournal of Nuclear Medicine 54(1) · November 2012with48 Reads
DOI: 10.2967/jnumed.112.109009 · Source: PubMed
Abstract
Unlabelled: (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). Methods: 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. Results: 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. Conclusion: 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.
    • "300-second frames measured 50 minutes after injection of 10 6 1.0 mCi of 18 F-Florbetapir AV-45. Global AV-45 PET values (gAV-45 PET) were obtained as an average of the image values within several large ROIs as previously described [23]. Preprocessing of the AV-45 PET scans and computation of the gAV-45 PET values were done centrally by the ADNI core (http://adni.loni.usc. "
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    • "As DS FDG and MRI scans were acquired using ADNI protocols and processed in the same manner, comparison was feasible. Subjects were considered Am2 if their amyloid PET cortical average standardized uptake value ratio (SUVR) was below a threshold of 1.47 for 11C-PiB [38] or ,1.11 for florbetapir [39] or their cerebrospinal fluid (CSF) Abeta42 was .209 (allowing for threshold variability ) and were considered Am1 if their amyloid PET SUVR exceeded threshold or their CSF Abeta42 level was ,192 [40]. "
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    • "In parallel, other Aβ PET tracers, [ 18 F]AV-45 (florbetapir; Amyvid, Eli Lily) and [ 18 F]AV-1 (florbetaben; Neuraceq, Piramal Imaging), have also been independently engineered from diaryl alkenes and are currently available for clinical diagnosis (Herholz and Ebmeier, 2011; Vallabhajosula, 2011). For the purpose of standardizing the difference of these Aβ PET tracers, several groups have investigated direct comparison of PET imaging data obtained by sequential scanning using several tracers in the same cohort (Vandenberghe et al., 2010; Wolk et al., 2012; Landau et al., 2013 Landau et al., , 2014). As for the cortical retention ratio of [ 11 C]PiB, both [ 18 F]3 ′ -FPiB and [ 18 F]AV-45 demonstrate a highly significant ability to discriminate between control subjects and AD patients, with a high linear correlation to the data obtained by [ 11 C]PiB. "
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