[18F]Flutemetamol amyloid-beta PET imaging compared with [11C]PIB across the spectrum of Alzheimer's disease.

PURPOSE: The aim was to identify the amyloid beta (Aß) deposition by positron emission tomography (PET) imaging with the (18)F-labeled Pittsburgh compound B (PIB) derivative [(18)F]flutemetamol (FMM) across a spectrum of Alzheimer's disease (AD) and to compare Aß deposition between [(18)F]FMM and [(11)C]PIB PET imaging. METHODS: The study included 36 patients with AD, 68 subjects with mild cognitive impairment (MCI), 41 older healthy controls (HC) (aged ≥56), 11 young HC (aged ≤45), and 10 transitional HC (aged 46-55). All 166 subjects underwent 30-min static [(18)F]FMM PET 85 min after injection, 60-min dynamic [(11)C]PIB PET, and cognitive testing. [(18)F]FMM scans were assessed visually, and standardized uptake value ratios (SUVR) were defined quantitatively in regions of interest identified on coregistered MRI (cerebellar cortex as a reference region). The PIB distribution volume ratios (DVR) were determined in the same regions. RESULTS: Of 36 AD patients, 35 had positive scans, while 36 of 41 older HC subjects had negative scans. [(18)F]FMM scans had a sensitivity of 97.2% and specificity of 85.3% in distinguishing AD patients from older HC subjects, and a specificity of 100% for young and transitional HC subjects. The [(11)C]PIB scan had the same results. Interreader agreement was excellent (kappa score = 0.81). The cortical FMM SUVR in AD patients was significantly greater than in older HC subjects (1.76 ± 0.23 vs 1.30 ± 0.26, p < 0.01). Of the MCI patients, 68 had a bimodal distribution of SUVR, and 29 of them (42.6%) had positive scans. Cortical FMM SUVR values were strongly correlated with PIB DVR (r = 0.94, n = 145, p < 0.001). CONCLUSION: [(18)F]FMM PET imaging detects Aß deposition in patients along the continuum from normal cognitive status to dementia of AD and discriminates AD patients from HC subjects, similar to [(11)C]PIB PET.

Longitudinal assessment of amyloid-beta deposition in initially amyloid-negative non-demented individuals with [11C]-PIB PET imaging.

ABSTRACT: This study aimed to assess the longitudinal changes in amyloid beta (Aß) deposition in cortical regions with [11C]-PIB PET in initially amyloid-negative non-demented subjects and evaluate whether amyloid-negative subjects convert to amyloid-positive.Sixteen cognitively normal (CN) and 7 mild cognitive impairment (MCI) subjects (aged 60-75 years), who were amyloid-negative at baseline, underwent 60-minute dynamic [11C]-PIB PET and cognitive assessment over 5.0 to 9.4 years of a long follow-up, and the apolipoprotein-E (APOE) genotype was assessed. Regions of interest were defined in the bilateral cortex on coregistered MRI. Quantitative analysis of [11C]-PIB was performed using the distribution value ratio (DVR). Longitudinal changes in global and regional PIB DVRs were evaluated in the same regions, and the annual rate of change in the PIB DVR was calculated.Seven (30.4%) of 23 initially amyloid-negative non-demented subjects converted to globally amyloid-positive (global PIB DVR ≥1.40) over a follow-up of 6.5 ±â€Š1.4 years (converter). The global PIB DVR in converters increased from 1.22 ±â€Š0.07 at baseline to 1.63 ±â€Š0.15 (n = 7, P < .01) at last follow-up, and an annual increase of global PIB DVR was 0.057 ±â€Š0.019/year (n = 7, P < .01). In contrast, the global PIB DVR in the remaining 16 subjects was 1.15 ±â€Š0.07 at baseline and did not change over a follow-up period (stable). The APOE ε4 allele was present in 4 (57.1%) of the 7 converters, differing from 2 (12.5%) of 16 stable subjects (Fisher's exact test, P < .05). Three amyloid-negative MCI subjects had an annual increase in global PIB DVR above 0.061/year and became positive at 2.8 ±â€Š0.5 years of follow-up, which was faster than 5.0 ±â€Š2.0 years in 4 CN subjects. The regional PIB DVR that increased early above the regional positivity threshold was most frequently found in the right lateral temporal cortex (71.4%), followed by the left frontal cortex (41.8%).Our results suggest that the initially amyloid-negative CN and MCI subjects, especially with APOE ε4, can become globally amyloid-positive over a longer time, based on early regional Aß deposition in the lateral temporal cortex and/or frontal cortex.

Amyloid ß deposition and glucose metabolism on the long-term progression of preclinical Alzheimer's disease.

AIM: Longitudinal changes in beta amyloid (Aß) deposition and glucose metabolism over a long-term progression of preclinical Alzheimer's disease (AD) were evaluated. METHODS: 22 preclinical AD subjects with amyloid-positive scans underwent [11C]-labeled Pittsburgh Compound-B (PIB) positron emission tomography (PET) and [18F]-fluorodeoxyglucose (FDG) PET imaging over 6.0 ± 1.8 years. A quantitative analysis of [11C]-PIB and [18F]-FDG was used with a standardized uptake value ratio (SUVR) in the same regions. RESULTS: In preclinical AD subjects, the cortical PIB SUVR was higher at baseline and increased at follow-up. 12 of the preclinical AD subjects progressed to mild cognitive impairment, six of whom had reduced glucose metabolism. The annual change in PIB SUVR was not related to that in FDG SUVR. CONCLUSION: Increases in Aß deposition lead to the progression to mild cognitive impairment, but decreases in glucose metabolism do not contribute to progression.

Longitudinal Assessment of Amyloid-ß Deposition by [18F]-Flutemetamol PET Imaging Compared With [11C]-PIB Across the Spectrum of Alzheimer's Disease.

This study evaluates the longitudinal changes in the amyloid-ß (Aß) deposition with [18F]-flutemetamol (FMM) PET imaging across the spectrum of Alzheimer's disease (AD), compared with [11C]-Pittsburgh Compound-B (PIB) PET. Eleven AD, 17 mild cognitive impairment (MCI) and 13 cognitively normal (CN) subjects underwent neuropsychological assessment and amyloid PET imaging using [18F]-FMM and [11C]-PIB during a follow-up period. Regions of interest were defined on co-registered MRI, and the FMM and PIB standardized uptake value ratio (SUVR) was used in the same cortical regions. The annual rate of change in FMM and PIB SUVRs was calculated. Cortical FMM SUVR in amyloid-positive subjects increased over a follow-up of 3.1 ± 0.5 years. An individual FMM SUVR was significantly correlated with PIB SUVR at baseline and at follow-up in the same AD, MCI, and CN subjects. The annual rate of increase in FMM SUVR was significantly greater in typical amyloid-positive (0.033 ± 0.023, n = 7), focal positive MCI (0.076 ± 0.034, n = 4) and positive CN (0.039 ± 0.027, n = 4) while that in AD (0.020 ± 0.018, n = 11) was smaller. Among amyloid-positive patients, the baseline FMM SUVR was inversely related with the increased rate in FMM SUVR (r=-0.44, n = 26, p < 0.05). An individual annual rate in change of cortical FMM SUVR was significantly correlated with that in cortical PIB SUVR. Our results suggest that the [18F]-FMM PET imaging can clarify the longitudinal assessment of Aß deposition across the AD spectrum, similarly to [11C]-PIB PET. The Increase in Aß deposition is faster in the predementia stage but not at a constant rate across the clinical stages of the AD spectrum.

Amyloid-ß Deposition and Long-Term Progression in Mild Cognitive Impairment due to Alzheimer's Disease Defined with Amyloid PET Imaging.

The aim was to evaluate brain amyloid-ß (Aß) deposition in patients with mild cognitive impairment (MCI) due to Alzheimer's disease (AD) using amyloid PET imaging and clarify the relationship between the annual change in Aß deposition and disease progression. Forty-eight MCI patients underwent neuropsychological assessment and amyloid PET imaging using [11C]-PIB over a follow-up of 5.7±1.5 years. Thirty-nine MCI patients who had an amyloid-positive scan were defined as MCI due to AD, and 9 MCI patients who had an amyloid-negative scan were included. Regions of interest were defined on co-registered MRI, and the PIB standardized uptake value ratio (SUVR) on the same regions was used over follow-up. Annual change in PIB SUVR was calculated. Patients with MCI due to AD had higher baseline PIB SUVR (1.81±0.32, n = 39, p < 0.01) and a greater annual rate of change in PIB SUVR (0.044±0.027, n = 39, p < 0.01) compared to amyloid-negative MCI patients. Twenty-eight (71.8%) progressed to AD. In patients who progressed during a short duration of 1.7±0.8 years, the annual rate of increase in PIB SUVR was 0.101±0.094 (n = 16, p < 0.05), which was greater compared to patients with long conversion or stable patients. There was a negative correlation between the annual rate of increase in PIB SUVR and duration of progression to AD among individual MCI converters (r = -0.47, n = 28, p < 0.05). The patients defined as MCI due to AD could progress to AD with a shorter period if they have a greater increased annual rate in brain Aß deposition.