@misc{oai:repo.qst.go.jp:00079742,
 author = {Shimada, Hitoshi and Kubota, Manabu and Takahata, Keisuke and Takado, Yuhei and Seki, Chie and Ono, Maiko and Sahara, Naruhiko and Kawamura, Kazunori and Ming-Rong, Zhang and Suhara, Tetsuya and Higuchi, Makoto and Shimada, Hitoshi and Kubota, Manabu and Takahata, Keisuke and Takado, Yuhei and Seki, Chie and Ono, Maiko and Sahara, Naruhiko and Kawamura, Kazunori and Ming-Rong, Zhang and Suhara, Tetsuya and Higuchi, Makoto},
 month = {Jul},
 note = {Background: Our previous studies demonstrated 18F-PM-PBB3 (18F-APN-1607) to be a promising PET ligand, with suitable pharmacokinetics, high contrast and minimal parenchymal off-target binding, for quantifying tau pathologies in Alzheimer’s disease (AD) and non-AD tauopathy patients. The present study aims to investigate the association between distribution pattern of PM-PBB3 and clinical features in patients with 4-repeat tauopathies.
Method: We enrolled 17 patients with 4-repeat tauopathies including clinically diagnosed progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and one patient with corticobasal degeneration (CBD) confirmed by brain biopsy. Seven AD spectrum patients, two Parkinson’s disease (PD) patients, and 15 cognitively healthy controls (HCs) were also recruited. All participants underwent PET scans with 18F-PM-PBB3 and 11C-PiB for estimating regional tau and amyloid-β (Aβ) loads. We generated parametric images of the standardized uptake value ratio (SUVR) to the cerebellar cortex for PM-PBB3 and PiB to evaluate brain regional tau and amyloid-βAβ loads.
Result: We confirmed that all patients with AD spectrum were PiB-positive, while all other participants were PiB-negative. 18F-PM-PBB3 PET showed a characteristic distribution pattern in patients with 4-repeat tauopathies, which was distinct from that observed in AD spectrum patients. Patients with 4-repeat tauopathies showed remarkable uptake of PM-PBB3 especially around subthalamic nucleus, basal ganglia, midbrain including nigra and red nucleus, and dentate nucleus, whereas PD patients did not show any prominent parenchymal uptake of PM-PBB3. Compared with PSP with Richardson syndrome, patients with other PSP-variants including PSP with progressive gait freezing, predominant parkinsonism, ocular motor dysfunction, and CBS/CBD showed relatively milder uptake of PM-PBB3 especially around the midbrain. In contrast, patients with 4-repeat tauopathies presenting behavioral and/or verbal symptoms also presented increased PM-PBB3 uptake in some cortices in addition to the above-mentioned regions. Interestingly, some cognitively healthy elderly showed elevated PM-PBB3 uptake with slight white matter atrophy, which resembled patients with 4-repeat tauopathies in terms of distribution pattern, despite the fact that they were PiB-negative and cognitively normal.
Conclusion: Our results support the hypothesis that distribution of PM-PBB3 may reflect clinical manifestations of 4-repeat tauopathies. 18F-PM-PBB3 PET may facilitate better understanding of the pathological basis of, and drug development for 4-repeat tau pathologies., The Alzheimer's Imaging Consortium (AIC2019)},
 title = {In vivo tracking of tau pathologies with 18F-PM-PBB3 (18F-APN-1607) PET in AD and diverse non-AD tauopathies},
 year = {2019}
}