Visual Assessment Versus Quantitative Assessment of ¹¹C-PIB PET and ¹⁸F-FDG PET for Detection of Alzheimer's Disease

Abstract

Amyloid-β (Aβ) imaging with N-methyl-¹¹C-2-(4′-methylamino-phenyl)-6-hydroxy-benzothiazole (¹¹C-6-OH-BTA-1; also known as ¹¹C-PIB) shows a robust increase in cortical binding in Alzheimer's disease (AD). The aim of this study was to explore the clinical potential of Aβ imaging for the diagnosis of AD by comparison of the accuracy of visual reading of ¹¹C-PIB images with quantitative analysis and ¹⁸F-FDG. Methods: Fifteen AD patients (age, 71.1 ± 11.3 y [mean ± SD]; mini-mental state examination [MMSE], 18.9 ± 9.3 [mean ± SD]) and 25 healthy control (HC) subjects (age, 71.9 ± 6.82 y; MMSE ≥ 28) underwent 90-min dynamic ¹¹C-PIB PET and 20-min static ¹⁸F-FDG PET. ¹¹C-PIB images, generated from data acquired between 40 and 70 min after injection, and ¹⁸F-FDG images were rated separately by 2 readers as normal, possible AD, or probable AD. Quantitative analyses used the distribution volume ratio (DVR) of frontal cortex, parietotemporal cortex, posterior cingulate, and caudate nucleus for ¹¹C-PIB and standardized uptake value ratio (SUVR) of parietotemporal cortex and posterior cingulate for ¹⁸F-FDG, using cerebellar cortex as the reference region. Receiver-operating-characteristic (ROC) analysis was performed to compare the accuracy of quantitative measures. To determine the effect of age on diagnostic accuracy, the median age of the AD subjects (74 y) was chosen to separate the cohort into younger (64.4 ± 5.8 y) and older (78.6 ± 4.1 y) groups. Results: Visual agreement between readers was excellent for ¹¹C-PIB (κ = 0.90) and good for ¹⁸F-FDG (κ = 0.56). ¹¹C-PIB was more accurate than ¹⁸F-FDG both on visual reading (accuracy, 90% vs. 70%, P = 0.05) and ROC analysis (95% vs. 83%, P = 0.02). Accuracy declined more with ¹⁸F-FDG than with ¹¹C-PIB in the older group. Conclusion: Visual analysis of ¹¹C-PIB images appears more accurate than visual reading of ¹⁸F-FDG for identification of AD and has accuracy similar to quantitative analysis of a 90-min dynamic scan. The accuracy of ¹¹C-PIB PET is limited by cortical binding in some healthy elderly subjects, consistent with postmortem studies of cerebral Aβ. Longitudinal follow-up is required to determine if this represents detection of preclinical AD.