Dataset Information

Quantitative evaluation of tau PET tracers 18F-THK5351 and 18F-AV-1451 in Alzheimer's disease with standardized uptake value peak-alignment (SUVP) normalization.

ABSTRACT: PURPOSE:Off-target binding in the reference region is a challenge for recent tau tracers 18F-AV-1451 and 18F-THK5351. The conventional standardized uptake value ratio (SUVR) method relies on the average uptake from an unaffected tissue sample, and therefore is susceptible to biases from off-target binding as well as variability among individuals in the reference region. We propose a new method, standardized uptake value peak-alignment (SUVP), to reduce the bias of the SUVR, and improve the quantitative assessment of tau deposition. METHODS:The SUVP normalizes uptake values by their mode and standard deviation. Instead of using a reference region, the SUVP derives the contrast from unaffected voxels over the whole brain. Using SUVP and SUVR methods, we evaluated the global and regional tau binding of 18F-THK5351 and 18F-AV-1451 on two independent cohorts (N?=?18 and 32, respectively), each with cognitively normal (NL) subjects and Alzheimer's disease (AD) subjects. RESULTS:Both tracers showed significantly increased binding for AD in the targeted cortical areas. In the temporal cortex, SUVP had a higher classification success rate (CSR) than SUVR (0.96 vs 0.89 for 18F-THK5351; 0.86 vs 0.75 for 18F-AV-1451), as well as higher specificity under fixed sensitivity around 0.80 (0.70 vs 0.45 specificity for 18F-THK5351; 1.00 vs 0.78 for 18F-AV-1451). In the cerebellar cortex, an AD-NL group difference with effect size (Cohen's d) of 0.62 was observed for AV-1451, confirming the limitation of the SUVR approach using this region as a reference. A smaller cerebellar effect size (0.09) was observed for THK5351. CONCLUSION:The SUVP method reduces the bias of the reference region and improves the NL-AD classification compared to the SUVR approach.

SUBMITTER: Chen J

PROVIDER: S-EPMC6174003 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Quantitative evaluation of tau PET tracers <sup>18</sup>F-THK5351 and <sup>18</sup>F-AV-1451 in Alzheimer's disease with standardized uptake value peak-alignment (SUVP) normalization.

Chen Jingyun J Li Yi Y Pirraglia Elizabeth E Okamura Nobuyuki N Rusinek Henry H de Leon Mony J MJ

European journal of nuclear medicine and molecular imaging 20180427 9

<h4>Purpose</h4>Off-target binding in the reference region is a challenge for recent tau tracers <sup>18</sup>F-AV-1451 and <sup>18</sup>F-THK5351. The conventional standardized uptake value ratio (SUVR) method relies on the average uptake from an unaffected tissue sample, and therefore is susceptible to biases from off-target binding as well as variability among individuals in the reference region. We propose a new method, standardized uptake value peak-alignment (SUVP), to reduce the bias of t ...[more]

PMID: 29704038

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Project description:BackgroundThe tau positron emission tomography (PET) ligand 18F-flortaucipir binds to paired helical filaments of tau in aging and Alzheimer's disease (AD), but its utility in detecting tau aggregates in frontotemporal dementia (FTD) is uncertain.MethodsWe performed 18F-flortaucipir imaging in patients with the FTD syndromes (n = 45): nonfluent variant primary progressive aphasia (nfvPPA) (n = 11), corticobasal syndrome (CBS) (n = 10), behavioral variant frontotemporal dementia (bvFTD) (n = 10), semantic variant primary progressive aphasia (svPPA) (n = 2) and FTD associated pathogenic genetic mutations microtubule-associated protein tau (MAPT) (n = 6), chromosome 9 open reading frame 72 (C9ORF72) (n = 5), and progranulin (GRN) (n = 1). All patients underwent MRI and β-amyloid biomarker testing via 11C-PiB or cerebrospinal fluid. 18F-flortaucipir uptake in patients was compared to 53 β-amyloid negative normal controls using voxelwise and pre-specified region of interest approaches.ResultsOn qualitative assessment, patients with nfvPPA showed elevated 18F-flortacupir binding in the left greater than right inferior frontal gyrus. Patients with CBS showed elevated binding in frontal white matter, with higher cortical gray matter uptake in a subset of β-amyloid-positive patients. Five of ten patients with sporadic bvFTD demonstrated increased frontotemporal binding. MAPT mutation carriers had elevated 18F-flortaucipir retention primarily, but not exclusively, in mutations with Alzheimer's-like neurofibrillary tangles. However, tracer retention was also seen in patients with svPPA, and the mutations C9ORF72, GRN predicted to have TDP-43 pathology. Quantitative region-of-interest differences between patients and controls were seen only in inferior frontal gyrus in nfvPPA and left insula and bilateral temporal poles in MAPT carriers. No significant regional differences were found in CBS or sporadic bvFTD. Two patients underwent postmortem neuropathological examination. A patient with C9ORF72, TDP-43-type B pathology, and incidental co-pathology of scattered neurofibrillary tangles in the middle frontal, inferior temporal gyrus showed corresponding mild 18F-flortaucipir retention without additional uptake matching the widespread TDP-43 type B pathology. A patient with sporadic bvFTD demonstrated punctate inferior temporal and hippocampus tracer retention, corresponding to the area of severe argyrophilic grain disease pathology.Conclusions18F-flortaucipir in patients with FTD and predicted tauopathy or TDP-43 pathology demonstrated limited sensitivity and specificity. Further postmortem pathological confirmation and development of FTD tau-specific ligands are needed.

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Dataset Information

Quantitative evaluation of tau PET tracers 18F-THK5351 and 18F-AV-1451 in Alzheimer's disease with standardized uptake value peak-alignment (SUVP) normalization.

Publications

Quantitative evaluation of tau PET tracers <sup>18</sup>F-THK5351 and <sup>18</sup>F-AV-1451 in Alzheimer's disease with standardized uptake value peak-alignment (SUVP) normalization.

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