Evaluation of 10-minute post-injection 11C-PiB PET and its correlation with 18F-FDG PET in older adults who are cognitively healthy, mildly impaired, or with probable Alzheimer's disease

Abstract

Objective: Positron emission tomography (PET) allows in vivo evaluation of molecular targets in neurodegenerative diseases, such as Alzheimer's disease. Mild cognitive impairment is an intermediate stage between normal cognition and Alzheimer-type dementia. In vivo fibrillar amyloid-beta can be detected in PET using [11C]-labeled Pittsburgh compound B (11C-PiB). In contrast, [18F]fluoro-2-deoxy-d-glucose (18F-FDG) is a neurodegeneration biomarker used to evaluate cerebral glucose metabolism, indicating neuronal injury and synaptic dysfunction. In addition, early cerebral uptake of amyloid-PET tracers can determine regional cerebral blood flow. The present study compared early-phase 11C-PiB and 18F-FDG in older adults without cognitive impairment, amnestic mild cognitive impairment, and clinical diagnosis of probable Alzheimer's disease.

Methods: We selected 90 older adults, clinically classified as healthy controls, with amnestic mild cognitive impairment, or with probable Alzheimer's disease, who underwent an 18F-FDG PET, early-phase 11C-PiB PET and magnetic resonance imaging. All participants were also classified as amyloid-positive or -negative in late-phase 11C-PiB. The data were analyzed using statistical parametric mapping.

Results: We found that the probable Alzheimer's disease and amnestic mild cognitive impairment group had lower early-phase 11C-PiB uptake in limbic structures than 18F-FDG uptake. The images showed significant interactions between amyloid-beta status (negative or positive). However, early-phase 11C-PiB appears to provide different information from 18F-FDG about neurodegeneration.

Conclusions: Our study suggests that early-phase 11C-PiB uptake correlates with 18F-FDG, irrespective of the particular amyloid-beta status. In addition, we observed distinct regional distribution patterns between both biomarkers, reinforcing the need for more robust studies to investigate the real clinical value of early-phase amyloid-PET imaging.

Keywords: Positron emission tomography; [11C]-labeled Pittsburgh compound B; [18F]fluoro-2-deoxy-d-glucose; aging; amyloid; cerebral glucose metabolism; neuroimaging; perfusion.

Figure 1. Maximum-intensity projections of Statistical Parametric Mapping software t-maps showing biodistribution differences between the positron emission tomography tracers. Areas of decreased ¹¹C-ePiB perfusion compared to ¹⁸F-FDG uptake in the groups appear in blue. Areas of increased ¹¹C-ePiB perfusion compared to ¹⁸F-FDG uptake appear in red. The significance threshold was p < 0.05, corrected by the family wise error method. ¹¹C-ePiB = early-phase [¹¹C]-labeled Pittsburgh compound B; ¹⁸F-FDG = [¹⁸F]fluoro-2-deoxy-d-glucose; R = right; L = left; A = anterior; P = posterior; S = superior; I = inferior; M = medial.

Figure 2. Correlation across brain regions between early-phase [¹¹C]-labeled Pittsburgh compound B (¹¹C-ePiB) and [¹⁸F]fluoro-2-deoxy-d-glucose (¹⁸F-FDG) in the control, mild cognitive impairment, and probable Alzheimer’s disease groups. The included areas are prefrontal, orbitofrontal, parietal, temporal, anterior and posterior cingulate, and the precuneus. Black circles and trendlines represent data from the ¹¹C-PiB-negative group, while pink circles and trendlines represent ¹¹C-PiB-positive group. Blue trendlines represent the combined groups (Aβ-negative and Aβ-positive). The authors created this illustration of meta-VOI in Biorender™ (https://biorender.com/).

Figure 3. Comparison between the probable Alzheimer’s disease group (n=27) and healthy controls (n=24) with both positron emission tomography tracers. A) Areas of significantly decreased early-phase [¹¹C]-labeled Pittsburgh compound B (¹¹C-ePiB) in the probable AD group are shown in blue, using volume-rendering images. B) Areas of decreased ¹¹C-ePiB perfusion are shown in blue, with the main coordinates visualized in statistical parametric mapping template ch2. C) Areas of decreased [¹⁸F]fluoro-2-deoxy-d-glucose (¹⁸F-FDG) uptake are shown in blue (volume-rendering visualization). D) Areas of decreased ¹⁸F-FDG uptake are shown in blue, with the main coordinates visualized in the statistical parametric mapping template ch2. The results were obtained through p < 0.05 family-wise error method correction at the cluster level, with a previous height threshold of p < 0.001. The color scale indicates T-score values generated in statistical parametric mapping.

Figure 4. Analysis of early-phase ¹¹C-ePiB PET (0-10 minutes) and ¹⁸F-FDG-PET uptake, based on amyloid-β biomarker status of ¹¹C-PiB PET (40-70 minutes). We studied 34 patients ¹¹C-PiB-positive (aMCI, n = 14 - probable AD, n = 20) and 32 patients ¹¹C-PiB-negative (aMCI, n = 25; probable Alzheimer’s disease, n = 7), vs. the healthy control group, which was ¹¹C-PiB-negative (n=19). A) Decreased ¹¹C-ePiB perfusion in amyloid-β ¹¹C-PiB-positive patients. B) Decreased ¹¹C-ePiB perfusion in amyloid-β [¹¹C]PiB-negative patients. C) Decreased ¹⁸F-FDG PET uptake in amyloid-β [¹¹C]PiB-positive patients. D) Decreased ¹⁸F-FDG PET uptake in amyloid-β ¹¹C-PiB-negative patients. The results were obtained using p < 0.05 family-wise error correction on the cluster level, with a previous height threshold of p < 0.001. The bars indicate z scores, ranging from p = 10^-3(z score = 3.0) to p = 10^-4 (z score = 4.0). ¹¹C-ePiB = early-phase [¹¹C]-labeled Pittsburgh compound B; ¹⁸F-FDG = [¹⁸F]fluoro-2-deoxy-d-glucose; aMCI: amnestic mild cognitive impairment group; PET = positron emission tomography.