18F-APN-1607 Tau Positron Emission Tomography Imaging for Evaluating Disease Progression in Alzheimer’s Disease

Abstract

Purpose18F-APN-1607 is a novel tau positron emission tomography (PET) tracer characterized with high binding affinity for 3− and 4-repeat tau deposits. The aim was to analyze the spatial distribution of 18F-APN-1607 PET imaging in Alzheimer’s disease (AD) subjects with different stages and to investigate the relationship between the change of tau deposition and overall disease progression.MethodsWe retrospectively analyzed the 18F-APN-1607 PET imaging of 31 subjects with clinically and imaging defined as AD. According to the Mini-Mental State Examination (MMSE) score, patients were divided into three groups, namely, mild (≥21, n = 7), moderate (10–20, n = 16), and severe (≤9, n = 8). PET imaging was segmented to 70 regions of interest (ROIs) and extracted the standard uptake value (SUV) of each ROI. SUV ratio (SUVR) was calculated from the ratio of SUV in different brain regions to the cerebellar cortex. The regions were defined as positive and negative with unsupervised cluster analysis according to SUVR. The SUVRs of each region were compared among groups with the one-way ANOVA or Kruskal–Wallis H test. Furthermore, the correlations between MMSE score and regional SUVR were calculated with Pearson or Spearman correlation analysis.ResultsThere were no significant differences among groups in gender (χ2 = 3.814, P = 0.161), age of onset (P = 0.170), age (P = 0.109), and education level (P = 0.065). With the disease progression, the 18F-APN-1607 PET imaging showed the spread of tau deposition from the hippocampus, posterior cingulate gyrus (PCG), and lateral temporal cortex (LTC) to the parietal and occipital lobes, and finally to the frontal lobe. Between the mild and moderate groups, the main brain areas with significant differences in 18F-APN-1607 uptake were supplementary motor area (SMA), cuneus, precuneus, occipital lobule, paracentral lobule, right angular gyrus, and parietal, which could be used for early disease progression assessment (P < 0.05). There were significant differences in the frontal lobe, right temporal lobe, and fusiform gyrus between the moderate and severe groups, which might be suitable for the late-stage disease progression assessment (P < 0.05).Conclusion18F-APN-1607 PET may serve as an effective imaging marker for visualizing the change pattern of tau protein deposition in AD patients, and its uptake level in certain brain regions is closely related to the severity of cognitive impairment. These indicate the potential of 18F-APN-1607 PET for the in vivo evaluation of the progression of AD.

Impact of white matter hyperintensities on subjective cognitive decline phenotype in a diverse cohort of cognitively normal older adults

“…The Guild Design performance is particularly relevant as we have recently shown that the right temporal lobe, which plays a role in visual working and associative memory, 34–38 is vulnerable to the combination of AD and small vessel disease 39 . Moreover, while faster progression has been linked to extensive WMH in the SCD stage, 40 it has also been associated with preferential right temporal neurodegeneration and tauopathy 41,42 …”

“…39 Moreover, while faster progression has been linked to extensive WMH in the SCD stage, 40 it has also been associated with preferential right temporal neurodegeneration and tauopathy. 41,42 This study has multiple strengths. Our cohort is larger and more racially and ethnically diverse than most other WMH studies at the SCD stage.…”

Characterizing Early-Onset Alzheimer Disease Using Multiprobe PET/MRI

“…The mean SUV (SUV mean ) and SUV ratio (SUVR) of each region were obtained as previously described. 20,21 β-Amyloid or tau PET and 18 F-FDG PET images were normalized using cerebellar cortex and whole-brain mean values, respectively. β-Amyloid PET imaging was carried out with 11 C-PIB or 18 F-AV45.…”

Synthesis and Bioevaluation of 2-Styrylquinoxaline Derivatives as Tau-PET Tracers

“…More importantly, the 2-phenylquinoxaline derivatives could interact with 4R-Tau on brain tissue from Tau-transgenic mice (rTg4510), overexpressing human 4R-Tau. According to the design strategy of the reported Tau tracers BF-126, [ 18 F]­FPPDB 15 , and [ 18 F]­APN-1607 , with diazene or ethylene moiety, in this study, a double bond was introduced between the quinoxaline and benzene ring to extend the molecular skeleton (Figure ). N,N -Dimethylamino, and N -monomethylamino substituents were attached to the 6-position on the quinoxaline moiety to ensure binding affinity and selectivity for Tau, while short FPEG chains were introduced into the phenyl ring to optimize pharmacokinetic properties and facilitate efficient 18 F-labeling .…”