Amyloid-ß PET Classification on Cognitive Aging Stages Using the Centiloid Scale.

PROPOSE: This study aims to explore the use of the Centiloid (CL) method in amyloid-ß PET quantification to evaluate distinct cognitive aging stages, investigating subjects' mismatch classification using different cut-points for amyloid-ß positivity. PROCEDURES: The CL equation was applied in four groups of individuals: SuperAgers (SA), healthy age-matched controls (AC), healthy middle-aged controls (MC), and Alzheimer's disease (AD). The amyloid-ß burden was calculated and compared between groups and quantitative variables. Three different cut-points (Jack CR, Wiste HJ, Weigand SD, et al., Alzheimer's Dement 13:205-216, 2017; Salvadó G, Molinuevo JL, Brugulat-Serrat A, et al., Alzheimer's Res Ther 11:27, 2019; and Amadoru S, Doré V, McLean CA, et al., Alzheimer's Res Ther 12:22, 2020) were applied in CL values to differentiate the earliest abnormal pathophysiological accumulation of Aß and the established Aß pathology. RESULTS: The AD group exhibited a significantly increased Aß burden compared to the MC, but not AC groups. Both healthy control (MC and AC) groups were not significantly different. Visually, the SA group showed a diverse distribution of CL values compared with MC; however, the difference was not significant. The CL values have a moderate and significant relationship between Aß visual read, RAVLT DR and MMSE. Depending on the cut-point used, 10 CL, 19 CL, or 30 CL, 7.5% of our individuals had a different classification in the Aß positivity. For the AC group, we obtained about 40 to 60% of the individuals classified as positive. CONCLUSION: SuperAgers exhibited a similar Aß load to AC and MC, differing in cognitive performance. Independently of cut-point used (10 CL, 19 CL, or 30 CL), three SA individuals were classified as Aß positive, showing the duality between the individual's clinics and the biological definition of Alzheimer's. Different cut-points lead to Aß positivity classification mismatch in individuals, and an extra care is needed for individuals who have a CL value between 10 and 30 CL.

Fully-automated radiosynthesis of the amyloid tracer [11C] PiB via direct [11C]CO2 fixation-reduction.

BACKGROUND: The ß-amyloid radiotracer [11C] PiB is extensively used for the Positron Emission Tomography (PET) diagnosis of Alzheimer's Disease and related dementias. For clinical use, [11C] PiB is produced using the 11C-methylation method ([11C] Methyl iodide or [11C] methyl triflate as 11C-methylation agents), which represents the most employed 11C-labelling strategy for the synthesis of 11C-radiopharmaceuticals. Recently, the use of direct [11C]CO2 fixation for the syntheses of 11C-tracers has gained interest in the radiochemical community due to its importance in terms of radiochemical versatility and for permitting the direct employment of the cyclotron-produced precursor [11C]CO2. This paper presents an optimised alternative one-pot methodology of [11C]CO2 fixation-reduction for the rapid synthesis of [11C] PiB using an automated commercial platform and its quality control. RESULTS: [11C] PiB was obtained from a (25.9 ± 13.2)% (Average ± Variation Coefficient, n = 3) (end of synthesis, decay corrected) radiochemical yield from trapped [11C]CO2 after 1 min of labelling time using PhSiH3 / TBAF as the fixation-reduction system in Diglyme at 150 °C. The radiochemical purity was higher than 95% in all cases, and the molar activity was (61.4 ± 1.6) GBq/µmol. The radiochemical yield and activity (EOS) of formulated [11C] PiB from cyclotron-produced [11C]CO2 was (14.8 ± 12.1)%, decay corrected) and 9.88 GBq (± 6.0%), respectively. These are higher values compared to that of the 11C-methylation method with [11C]CH3OTf (~ 8.3%). CONCLUSIONS: The viability of the system PhSiH3 / TBAF to efficiently promote the radiosynthesis of [11C] PiB via direct [11C]CO2 fixation-reduction has been demonstrated. [11C] PiB was obtained through a fully automated radiosynthesis with a satisfactory yield, purity and molar activity. According to the results, the one-pot methodology employed could reliably yield sufficiently high tracer amounts for preclinical and clinical use.

Concordance between 11C-PIB-PET and clinical diagnosis in a memory clinic.

INTRODUCTION: Today, ligands that bind to fibrillar ß-amyloid are detectable by Positron Emission Tomography (PET) allowing for in vivo visualization for Abeta burden. However, amyloid plaques detection per se does not establish Alzheimer's Disease diagnosis. In this sense, the utility of amyloid imaging to improve clinical diagnosis was settled only for specific clinical scenarios and few studies have assessed amyloid molecular neuroimaging in a broader clinical setting. The aim of this study is to determine the frequency of PiB amyloid findings in different diagnostic syndromes grouped into high and low probability pre- test categories, taking into account pre-test clinical assumption of the presence of AD related pathology. METHODS: 144 patients were assigned into categories of high or low pretest probability according to clinical suspicion of AD pathology. The high probability group included: amnestic Mild Cognitive Impairment (MCI), amnestic and other domains MCI, Dementia of Alzheimer's Type (DAT), Posterior Cortical Atrophy (PCA), logopenic Primary Progressive Aphasia (PPA), Cerebral Amyloid Angiopathy and mixed dementia. The low assumption group included: normal controls, non-amnestic MCI, non-logopenic PPA and Frontotemporal Dementia (FTD). RESULTS: Only normal controls and DAT patients (typical and atypical presentation) were the most consistent across clinical and molecular diagnostics. MCI, non-logopenic PPA and FTD were the syndromic diagnoses that most discrepancies were found. DISCUSSION: This study demonstrates that detecting in vivo amyloid plaques by molecular imaging is considerably frequent in most of the dementia syndromes and shows that there are frequent discordance between molecular diagnosis and clinical assumption.