Preclinical Characterization of the Tau PET Tracer [18F]SNFT-1: Comparison of Tau PET Tracers

• DOI: 10.2967/jnumed.123.265593
• Publication Date: 2023-06-15T16:50:23Z
• Authors: Ryuichi Harada; Pradith Lerdsirisuk; Yuki Shimizu; Yuka Yokoyama; Yiqing Du; Kaede Kudo; Michinori Ezura; Yoichi Ishikawa; Ren Iwata; Miho Shidahara; Aiko Ishiki; Akio Kikuchi; Yuya Hatano; Tomohiko Ishihara; Osamu Onodera; Yasushi Iwasaki; Mari Yoshida; Yasuyuki Taki; Hiroyuki Arai; Yukitsuka Kudo; Kazuhiko Yanai; Shozo Furumoto; Nobuyuki Okamura
• Keywords: Monoamine oxidase B; Monoamine oxidase A

Tau PET tracers are expected to be sufficiently sensitive track the progression of age-related tau pathology in medial temporal cortex. The tracer <i>N</i>-(4-[¹⁸F]fluoro-5-methylpyridin-2-yl)-7-aminoimidazo[1,2-a]pyridine ([¹⁸F]SNFT-1) has been successfully developed by optimizing imidazo[1,2-a]pyridine derivatives. We characterized binding properties [¹⁸F]SNFT-1 using a head-to-head comparison with other reported ¹⁸F-labeled tracers. <b>Methods:</b> affinity SNFT-1 tau, amyloid, and monoamine oxidase A B was compared that second-generation MK-6240, PM-PBB3, PI-2620, RO6958948, JNJ-64326067, flortaucipir. In vitro were evaluated through autoradiography frozen human brain tissues from patients diverse neurodegenerative disease spectra. Pharmacokinetics, metabolism, radiation dosimetry assessed normal mice after intravenous administration [¹⁸F]SNFT-1. <b>Results:</b> assays demonstrated possesses high selectivity for aggregates Alzheimer (AD) brains. Autoradiographic analysis deposits sections AD showed higher signal-to-background ratio than no significant non-AD α-synuclein, transactiviation response DNA-binding protein-43, transmembrane protein 106B sections. Furthermore, did not bind significantly various receptors, ion channels, or transporters. initial uptake rapid washout brains without radiolabeled metabolites. <b>Conclusion:</b> These preclinical data suggest is promising selective radiotracer candidate allows quantitative monitoring accumulation brain.