PT  - JOURNAL ARTICLE
AU  - Harada, Ryuichi
AU  - Hayakawa, Yoshimi
AU  - Ezura, Michinori
AU  - Lerdsirisuk, Pradith
AU  - Du, Yiqing
AU  - Ishikawa, Yoichi
AU  - Iwata, Ren
AU  - Shidahara, Miho
AU  - Ishiki, Aiko
AU  - Kikuchi, Akio
AU  - Arai, Hiroyuki
AU  - Kudo, Yukitsuka
AU  - Yanai, Kazuhiko
AU  - Furumoto, Shozo
AU  - Okamura, Nobuyuki
TI  - <sup>18</sup>F-SMBT-1: A Selective and Reversible PET Tracer for Monoamine Oxidase-B Imaging
AID  - 10.2967/jnumed.120.244400
DP  - 2021 Feb 01
TA  - Journal of Nuclear Medicine
PG  - 253--258
VI  - 62
IP  - 2
4099  - http://jnm.snmjournals.org/content/62/2/253.short
4100  - http://jnm.snmjournals.org/content/62/2/253.full
SO  - J Nucl Med2021 Feb 01; 62
AB  - Reactive astrocytes play a key role in the pathogenesis of various neurodegenerative diseases. Monoamine oxidase-B (MAO-B) is one of the promising targets for the imaging of astrogliosis in the human brain. A novel selective and reversible MAO-B tracer, (S)-(2-methylpyrid-5-yl)-6-[(3-18F-fluoro-2-hydroxy)propoxy]quinoline (18F-SMBT-1), was successfully developed via lead optimization from the first-generation tau PET tracer 18F-THK-5351. Methods: SMBT-1 was radiolabeled with 18F using the corresponding precursor. The binding affinity of radiolabeled compounds to MAO-B was assessed using saturation and competitive binding assays. The binding selectivity of 18F-SMBT-1 to MAO-B was evaluated by autoradiography of frozen human brain tissues. The pharmacokinetics and metabolism were assessed in normal mice after intravenous administration of 18F-SMBT-1. A 14-d toxicity study after the intravenous administration of 18F-SMBT-1 was performed using rats and mice. Results: In vitro binding assays demonstrated a high binding affinity of 18F-SMBT-1 to MAO-B (dissociation constant, 3.7 nM). In contrast, it showed low binding affinity to MAO-A and protein aggregates such as amyloid-β and tau fibrils. Autoradiographic analysis showed higher amounts of 18F-SMBT-1 binding in the Alzheimer disease brain sections than in the control brain sections. 18F-SMBT-1 binding was completely displaced with the reversible MAO-B inhibitor lazabemide, demonstrating the high selectivity of 18F-SMBT-1 for MAO-B. Furthermore, 18F-SMBT-1 showed a high uptake by brain, rapid washout, and no radiolabeled metabolites in the brain of normal mice. 18F-SMBT-1 showed no significant binding to various receptors, ion channels, or transporters, and no toxic effects related to its administration were observed in mice and rats. Conclusion: 18F-SMBT-1 is a promising and selective MAO-B PET tracer candidate, which would be useful for quantitative monitoring of astrogliosis in the human brain.