Exploratory Tau PET/CT with [11C]PBB3 in Patients with Suspected Alzheimer's Disease and Frontotemporal Lobar Degeneration: A Pilot Study on Correlation with PET Imaging and Cerebrospinal Fluid Biomarkers.

Accurately diagnosing Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) is challenging due to overlapping symptoms and limitations of current imaging methods. This study investigates the use of [11C]PBB3 PET/CT imaging to visualize tau pathology and improve diagnostic accuracy. Given diagnostic challenges with symptoms and conventional imaging, [11C]PBB3 PET/CT's potential to enhance accuracy was investigated by correlating tau pathology with cerebrospinal fluid (CSF) biomarkers, positron emission tomography (PET), computed tomography (CT), amyloid-beta, and Mini-Mental State Examination (MMSE). We conducted [11C]PBB3 PET/CT imaging on 24 patients with suspected AD or FTLD, alongside [11C]PiB PET/CT (13 patients) and [18F]FDG PET/CT (15 patients). Visual and quantitative assessments of [11C]PBB3 uptake using standardized uptake value ratios (SUV-Rs) and correlation analyses with clinical assessments were performed. The scans revealed distinct tau accumulation patterns; 13 patients had no or faint uptake (PBB3-negative) and 11 had moderate to pronounced uptake (PBB3-positive). Significant inverse correlations were found between [11C]PBB3 SUV-Rs and MMSE scores, but not with CSF-tau or CSF-amyloid-beta levels. Here, we show that [11C]PBB3 PET/CT imaging can reveal distinct tau accumulation patterns and correlate these with cognitive impairment in neurodegenerative diseases. Our study demonstrates the potential of [11C]PBB3-PET imaging for visualizing tau pathology and assessing disease severity, offering a promising tool for enhancing diagnostic accuracy in AD and FTLD. Further research is essential to validate these findings and refine the use of tau-specific PET imaging in clinical practice, ultimately improving patient care and treatment outcomes.

Quantitative analysis of regional distribution of tau pathology with 11C-PBB3-PET in a clinical setting.

PURPOSE: The recent developments of tau-positron emission tomography (tau-PET) enable in vivo assessment of neuropathological tau aggregates. Among the tau-specific tracers, the application of 11C-pyridinyl-butadienyl-benzothiazole 3 (11C-PBB3) in PET shows high sensitivity to Alzheimer disease (AD)-related tau deposition. The current study investigates the regional tau load in patients within the AD continuum, biomarker-negative individuals (BN) and patients with suspected non-AD pathophysiology (SNAP) using 11C-PBB3-PET. MATERIALS AND METHODS: A total of 23 memory clinic outpatients with recent decline of episodic memory were examined using 11C-PBB3-PET. Pittsburg compound B (11C-PIB) PET was available for 17, 18F-flurodeoxyglucose (18F-FDG) PET for 16, and cerebrospinal fluid (CSF) protein levels for 11 patients. CSF biomarkers were considered abnormal based on Aß42 (< 600 ng/L) and t-tau (> 450 ng/L). The PET biomarkers were classified as positive or negative using statistical parametric mapping (SPM) analysis and visual assessment. Using the amyloid/tau/neurodegeneration (A/T/N) scheme, patients were grouped as within the AD continuum, SNAP, and BN based on amyloid and neurodegeneration status. The 11C-PBB3 load detected by PET was compared among the groups using both atlas-based and voxel-wise analyses. RESULTS: Seven patients were identified as within the AD continuum, 10 SNAP and 6 BN. In voxel-wise analysis, significantly higher 11C-PBB3 binding was observed in the AD continuum group compared to the BN patients in the cingulate gyrus, tempo-parieto-occipital junction and frontal lobe. Compared to the SNAP group, patients within the AD continuum had a considerably increased 11C-PBB3 uptake in the posterior cingulate cortex. There was no significant difference between SNAP and BN groups. The atlas-based analysis supported the outcome of the voxel-wise quantification analysis. CONCLUSION: Our results suggest that 11C-PBB3-PET can effectively analyze regional tau load and has the potential to differentiate patients in the AD continuum group from the BN and SNAP group.

Comparison of MRI-based and PET-based image pre-processing for quantification of 11C-PBB3 uptake in human brain.

PURPOSE: Quantification of tau load using 11C-PBB3-PET has the potential to improve diagnosis of neurodegenerative diseases. Although MRI-based pre-processing is used as a reference method, not all patients have MRI. The feasibility of a PET-based pre-processing for the quantification of 11C-PBB3 tracer was evaluated and compared with the MRI-based method. MATERIALS AND METHODS: Fourteen patients with decreased recent memory were examined with 11C-PBB3-PET and MRI. The PET scans were visually assessed and rated as either PBB3(+) or PBB3(-). The image processing based on the PET-based method was validated against the MRI-based approach. The regional uptakes were quantified using the Mesial-temporal/Temporoparietal/Rest of neocortex (MeTeR) regions. SUVR values were calculated by normalizing to the cerebellar reference region to compare both methods within the patient groups. RESULTS: Significant correlations were observed between the SUVRs of the MRI-based and the PET-based methods in the MeTeR regions (rMe=0.91; rTe=0.98; rR=0.96; p<0.0001). However, the Bland-Altman plot showed a significant bias between both methods in the subcortical Me region (bias: -0.041; 95% CI: -0.061 to -0.024; p=0.003). As in the MRI-based method, the 11C-PBB3 uptake obtained with the PET-based method was higher for the PBB3(+) group in each of the cortical regions and for the whole brain than for the PBB3(-) group (PET-basedGlobal: 1.11 vs. 0.96; Cliff's Delta (d)=0.68; p=0.04; MRI-basedGlobal: 1.11 vs. 0.97; d=0.70; p=0.03). To differentiate between positive and negative scans, Youden's index estimated the best cut-off of 0.99 from the ROC curve with good accuracy (AUC: 0.88±0.10; 95% CI: 0.67-1.00) and the same sensitivity (83%) and specificity (88%) for both methods. CONCLUSION: The PET-based pre-processing method developed to quantify the tau burden with 11C-PBB3 provided comparable SUVR values and effect sizes as the MRI-based reference method. Furthermore, both methods have a comparable discrimination accuracy between PBB3(+) and PBB3(-) groups as assessed by visual rating. Therefore, the presented PET-based method can be used for clinical diagnosis if no MRI image is available.