RT Journal Article
SR Electronic
T1 Preclinical Characterization of the Tau PET Tracer [<sup>18</sup>F]SNFT-1: Comparison of Tau PET Tracers
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1495
OP 1501
DO 10.2967/jnumed.123.265593
VO 64
IS 9
A1 Harada, Ryuichi
A1 Lerdsirisuk, Pradith
A1 Shimizu, Yuki
A1 Yokoyama, Yuka
A1 Du, Yiqing
A1 Kudo, Kaede
A1 Ezura, Michinori
A1 Ishikawa, Yoichi
A1 Iwata, Ren
A1 Shidahara, Miho
A1 Ishiki, Aiko
A1 Kikuchi, Akio
A1 Hatano, Yuya
A1 Ishihara, Tomohiko
A1 Onodera, Osamu
A1 Iwasaki, Yasushi
A1 Yoshida, Mari
A1 Taki, Yasuyuki
A1 Arai, Hiroyuki
A1 Kudo, Yukitsuka
A1 Yanai, Kazuhiko
A1 Furumoto, Shozo
A1 Okamura, Nobuyuki
YR 2023
UL http://jnm.snmjournals.org/content/64/9/1495.abstract
AB Tau PET tracers are expected to be sufficiently sensitive to track the progression of age-related tau pathology in the medial temporal cortex. The tau PET tracer N-(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 the binding properties of [18F]SNFT-1 using a head-to-head comparison with other reported 18F-labeled tau tracers. Methods: The binding affinity of SNFT-1 to tau, amyloid, and monoamine oxidase A and B was compared with that of the second-generation tau tracers MK-6240, PM-PBB3, PI-2620, RO6958948, JNJ-64326067, and flortaucipir. In vitro binding properties of 18F-labeled tau tracers were evaluated through the autoradiography of frozen human brain tissues from patients with diverse neurodegenerative disease spectra. Pharmacokinetics, metabolism, and radiation dosimetry were assessed in normal mice after intravenous administration of [18F]SNFT-1. Results: In vitro binding assays demonstrated that [18F]SNFT-1 possesses high selectivity and high affinity for tau aggregates in Alzheimer disease (AD) brains. Autoradiographic analysis of tau deposits in medial temporal brain sections from patients with AD showed a higher signal-to-background ratio for [18F]SNFT-1 than for the other tau PET tracers and no significant binding with non-AD tau, α-synuclein, transactiviation response DNA-binding protein-43, and transmembrane protein 106B aggregates in human brain sections. Furthermore, [18F]SNFT-1 did not bind significantly to various receptors, ion channels, or transporters. [18F]SNFT-1 showed a high initial brain uptake and rapid washout from the brains of normal mice without radiolabeled metabolites. Conclusion: These preclinical data suggest that [18F]SNFT-1 is a promising and selective tau radiotracer candidate that allows the quantitative monitoring of age-related accumulation of tau aggregates in the human brain.