Article
作者: Kawamura, Kazunori ; Takahata, Keisuke ; Fujinaga, Masayuki ; Yamaguchi, Yoshiki ; Suhara, Tetsuya ; Kokubo, Naomi ; Takuwa, Hiroyuki ; Tagai, Kenji ; Ono, Maiko ; Matsuoka, Kiwamu ; Kumata, Katsushi ; Mimura, Koki ; Nagai, Yuji ; Shimada, Hitoshi ; Takahashi, Manami ; Seki, Chie ; Shimozawa, Aki ; Endo, Hironobu ; Kimura, Yasuyuki ; Shinotoh, Hitoshi ; Zhang, Ming-Rong ; Shimizu, Hiroshi ; Kakita, Akiyoshi ; Kikuchi, Tatsuya ; Hasegawa, Masato ; Hirata, Kosei ; Minamimoto, Takafumi ; Ichise, Masanori ; Higuchi, Makoto ; Takado, Yuhei ; Mishra, Sushil K ; Sahara, Naruhiko ; Kataoka, Yuko ; Mori, Wakana
Deposition of α-synuclein fibrils is implicated in Parkinson's disease (PD) and dementia with Lewy bodies (DLB), while in vivo detection of α-synuclein pathologies in these illnesses has been challenging. Here, we have developed a small-molecule ligand, C05-05, for visualizing α-synuclein deposits in the brains of living subjects. In vivo optical and positron emission tomography (PET) imaging of mouse and marmoset models demonstrated that C05-05 captured a dynamic propagation of fibrillogenesis along neural pathways, followed by disruptions of these structures. High-affinity binding of 18F-C05-05 to α-synuclein aggregates in human brain tissues was also proven by in vitro assays. Notably, PET-detectable 18F-C05-05 signals were intensified in the midbrains of PD and DLB patients as compared with healthy controls, providing the first demonstration of visualizing α-synuclein pathologies in these illnesses. Collectively, we propose a new imaging technology offering neuropathology-based translational assessments of PD and allied disorders toward diagnostic and therapeutic research and development.
