Using PET with 18F-AV-45 (florbetapir) to quantify brain amyloid load in a clinical environment

Abstract

PurposePositron emission tomography (PET) imaging of brain amyloid load has been suggested as a core biomarker for Alzheimer’s disease (AD). The aim of this study was to test the feasibility of using PET imaging with 18F-AV-45 (florbetapir) in a routine clinical environment to differentiate between patients with mild to moderate AD and mild cognitive impairment (MCI) from normal healthy controls (HC).MethodsIn this study, 46 subjects (20 men and 26 women, mean age of 69.0 ± 7.6 years), including 13 with AD, 12 with MCI and 21 HC subjects, were enrolled from three academic memory clinics. PET images were acquired over a 10-min period 50 min after injection of florbetapir (mean ± SD of radioactivity injected, 259 ± 57 MBq). PET images were assessed visually by two individuals blinded to any clinical information and quantitatively via the standard uptake value ratio (SUVr) in the specific regions of interest, which were defined in relation to the cerebellum as the reference region.ResultsThe mean values of SUVr were higher in AD patients (median 1.20, Q1-Q3 1.16-1.30) than in HC subjects (median 1.05, Q1-Q3 1.04-1.08; p = 0.0001) in the overall cortex and all cortical regions (precuneus, anterior and posterior cingulate, and frontal median, temporal, parietal and occipital cortex). The MCI subjects also showed a higher uptake of florbetapir in the posterior cingulate cortex (median 1.06, Q1-Q3 0.97-1.28) compared with HC subjects (median 0.95, Q1-Q3 0.82-1.02; p = 0.03). Qualitative visual assessment of the PET scans showed a sensitivity of 84.6% (95% CI 0.55–0.98) and a specificity of 38.1% (95% CI 0.18–0.62) for discriminating AD patients from HC subjects; however, the quantitative assessment of the global cortex SUVr showed a sensitivity of 92.3% and specificity of 90.5% with a cut-off value of 1.122 (area under the curve 0.894).ConclusionThese preliminary results suggest that PET with florbetapir is a safe and suitable biomarker for AD that can be used routinely in a clinical environment. However, the low specificity of the visual PET scan assessment could be improved by the use of specific training and automatic or semiautomatic quantification tools.

Use of Standardized Uptake Value Ratios Decreases Interreader Variability of [18F] Florbetapir PET Brain Scan Interpretation

“…This value of 0.69 is similar to the value in another study with 5 readers visually assessing 59 cases ( ϭ 0.76) and in a study with 2 readers visually assessing 46 cases ( ϭ 0.71). 17 The values of our study are also similar to those seen with other ␤-amyloid imaging agents such as 11 C Pittsburgh compound-B. 26 The impact of the data of SUVr on values reported here is also higher than those seen in interobserver variability studies in lesion detection in other organ systems, for example, in the detection of pulmonary nodules with ( ϭ 0.67) 27 and without the use of computer-assisted detection software ( ϭ 0.64) 28 and the detection of breast lesions by using automatic breast scanners ( ϭ 0.8).…”

“…Cortex-to-wholecerebellum SUVr values were automatically calculated and presented by the software for 6 anatomically relevant cortical ROIs: frontal lobe, lateral parietal lobe, lateral temporal lobe, precuneus, and anterior and posterior cingulate gyrus, as well as the mean SUVr of these regions. 12 Prior studies demonstrated that with the aid of the average SUVr from these anatomic regions, sensitivity and specificity of reads increased by using both clinical diagnosis 17 and pathology 7 as comparisons. Although we chose to use the Scenium software to calculate SUVr, commercial programs from other vendors are available for calculating SUVr.…”

Quantification of Blood Flow-Dependent Component in Estimates of Beta-Amyloid Load Obtained Using Quasi-Steady-State Standardized Uptake Value Ratio

“…18,19 This approach provides data for calculation of the SUVR between amyloid-rich target regions and an amyloid-free reference region. In the standard quantification procedure, the regional radioactivity concentration is first converted to standardized uptake values (SUVs) typically by a global normalization involving a division with total injected radioactivity and multiplication with body weight.…”

Quantitation of PET signal as an adjunct to visual interpretation of florbetapir imaging

“…It has been suggested that image quantitation could be helpful in assisting visual interpretation of PET amyloid images [10][11][12][13]. Quantitation has been applied extensively in other realms of nuclear medicine imaging including PET [14][15][16][17], and quantitative analyses have proven useful for characterizing amyloid tracer binding and relationships to other biomarkers [18][19][20].…”