The Imaging Features and Clinical Associations of a Novel Tau PET Tracer—18F-APN1607 in Alzheimer Disease

Abstract

Purpose of the Report In vivo tau PET imaging could help clarify the spatial distribution of tau deposition in Alzheimer disease (AD) and aid in the differential diagnosis of tauopathies. To date, there have been no in vivo 18F-APN1607 tau PET studies in patients with AD. Methods We applied tau tracer in 12 normal controls (NCs) and 10 patients in the mild to moderate stage of probable AD. Detailed clinical information, cognitive measurements, and disease severity were documented. Regional SUV ratios (SUVRs) from 18F-AV-45 (florbetapir), 18F-APN1607 PET images, and regional gray matter (GM) atrophic ratios were calculated for further analysis. Results Quantitative analyses showed significantly elevated SUVRs in the frontal, temporal, parietal, occipital lobes, anterior and posterior cingulate gyri, precuneus, and parahippocampal region (all P’s < 0.01) with medium to large effect sizes (0.44–0.75). The SUVRs from 18F-APN1607 PET imaging showed significant correlations with the Alzheimer’s Disease Assessment Scale (ADAS-cog) scores (all P’s < 0.01) and strong correlation coefficients (R 2 ranged from 0.54 to 0.68), even adjusted for age and sex effects. Finally, the SUVRs from 18F-APN1607 PET imaging of the parahippocampal region showed rapid saturation as the ADAS-cog scores increased, and the SUVRs of the posterior cingulate gyrus and the temporal, frontal, parietal, and occipital regions slowly increased. The combined SUVRs from amyloid, tau PET, and regional GM atrophic ratio showed regional specific patterns as the ADAS-cog scores increased. Conclusions Our findings suggest that the 18F-APN1607 tau tracer correlated well with cognitive changes and demonstrated the spatial pattern of amyloid, tau deposition, and GM atrophy in the progression of AD.

TauIQ: A Canonical Image Based Algorithm to Quantify Tau PET Scans

“…[ 18 F]GTP-1(7), [ 18 F]RO-948(8), [ 18 F]PI-2620 (9) and [ 18 F]APN-1607 (10) and in May 2020 [ 18 F]Flortaucipir was FDA approved as a radioactive diagnostic agent for adult patients with cognitive impairment who are being evaluated for Alzheimer's disease (11,12).…”

Clinical validity of increased cortical binding of tau ligands of the THK family and PBB3 on PET as biomarkers for Alzheimer’s disease in the context of a structured 5-phase development framework

“…A fluorinated derivative of PBB3 ( 11 C-labeled) with somewhat different pharmacological properties has now been developed (i.e., 18 F-APN-1607) and is intended to substitute the original ligand [71]. Hopefully, the longer half-life of 18 F would allow the thorough investigation of the ligand and the emergence of replication studies, something that was limited with PBB3 since most of the evidence derives from the original developers of the ligand.…”

PET Neuroimaging of Alzheimer's Disease: Radiotracers and Their Utility in Clinical Research

“…Minor structural modifications then afforded [ 18 F]APN-1607 (PM-PBB3) and [ 18 F]AM-PBB3, the next generation members of the PBB3 family. [ 18 F]APN-1607, ( Figure 2 ) has recently been reported to possess more favorable pharmacokinetics and provide higher gray-matter/white-matter contrast (Hsu et al, 2020 ; Su et al, 2020 ; Tagai et al, 2021 ).…”