Abstract
Molecular imaging of tauopathies is complicated by the differing specificities and off-target binding properties of available radioligands for positron emission tomography (PET). [18F]-APN-1607 ([18F]-PM-PBB3) is a newly developed PET tracer with promising properties for tau imaging. We aimed to characterize the cerebral binding of [18F]-APN-1607 in Alzheimer’s disease (AD) patients compared to normal control (NC) subjects. Therefore, we obtained static late frame PET recordings with [18F]-APN-1607 and [18F]-FDG in patients with a clinical diagnosis of AD group, along with an age-matched NC group ([18F]-APN-1607 only). Using statistical parametric mapping (SPM) and volume of interest (VOI) analyses of the reference region normalized standardized uptake value ratio maps, we then tested for group differences and relationships between both PET biomarkers, as well as their associations with clinical general cognition. In the AD group, [18F]-APN-1607 binding was elevated in widespread cortical regions (P < 0.001 for VOI analysis, familywise error-corrected P < 0.01 for SPM analysis). The regional uptake in AD patients correlated negatively with Mini-Mental State Examination score (frontal lobe: R = -0.632, P = 0.004; temporal lobe: R = -0.593, P = 0.008; parietal lobe: R = -0.552, P = 0.014; insula: R = -0.650, P = 0.003; cingulum: R = -0.665, P = 0.002) except occipital lobe (R = -0.417, P = 0.076). The hypometabolism to [18F]-FDG PET in AD patients also showed negative correlations with regional [18F]-APN-1607 binding in some signature areas of AD (temporal lobe: R = -0.530, P = 0.020; parietal lobe: R = -0.637, P = 0.003; occipital lobe: R = -0.567, P = 0.011). In conclusion, our results suggested that [18F]-APN-1607 PET sensitively detected tau deposition in AD and that individual tauopathy correlated with impaired cerebral glucose metabolism and cognitive function.
Highlights
The hyperphosphorylated, aggregated tau that comprises intracellular filamentous inclusions is implicated in a number of neurodegenerative pathologies (Spillantini and Goedert, 2013)
The general cognition of the Alzheimer’s disease (AD) group as assessed by Clinical Dementia Rating (CDR)-Global Score (CDR-GS) and Mini-Mental State Examination (MMSE) score showed that our patient cohort was mainly at moderate to advanced stages of the disease (CDR-GS: 1 (1–2); MMSE: 17.0 ± 7.6)
Our main objective was to characterize the utility of this nextgeneration tau tracer in terms of effect size for detecting diseasespecific tau deposition, confirming the known relationship between tau deposition and decreased FDG uptake and cognitive impairment in AD patients
Summary
The hyperphosphorylated, aggregated tau that comprises intracellular filamentous inclusions is implicated in a number of neurodegenerative pathologies (Spillantini and Goedert, 2013). Of the normally unfolded microtubule-associated protein tau into a highly structured amyloid fibril is implicated in the pathological process underlying human tauopathies (Goedert et al, 2017). [11C]-THK5351 binding matched the tau pathology expected for AD, whereas [11C]-PBB3 binding showed a greater affiliation with β-amyloid distribution (Chiotis et al, 2018). Further quantitative autoradiographic analysis post-mortem showed moderate [11C]-PBB3 autoradiographic binding vs relatively faint [18F]-AV-1451 labeling of the 3R isoforms in brains of patients dying with Pick’s disease (PiD), and likewise for the 4R isoforms in brains of patients dying with progressive supranuclear palsy (PSP) or corticobasal degeneration. The binding of the two ligands was similar for paired helical filament (PHF)-tau in patients dying with AD (Ono et al, 2017)
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