title: Synthesis and evaluation of ¹⁸F-labeled styryltriazole and resveratrol derivatives for β-amyloid plaque imaging.
abstract: In the present study, a styryltriazole and four resveratrol derivatives were synthesized as candidates for β-amyloid (Aβ) plaque imaging. On the basis of their binding affinities to Aβ(1-42) aggregates, the styryltriazole (1, K(i) = 12.8 nM) and one resveratrol derivative (5, K(i) = 0.49 nM) were labeled with (18)F. In normal mice, tissue distribution of [(18)F]5 showed good initial brain uptake (3.26% ID/g at 2 min) but slow wash-out from brains (2-to-60 min uptake ratio: 2.9). Furthermore, it underwent in vivo metabolic defluorination (1.88% ID/g at 2 min and 9.73% ID/g at 60 min). In contrast, [(18)F]1 displayed high initial brain uptake (5.38% ID/g at 2 min) with rapid wash-out from brains (0.52% ID/g at 60 min; 2-to-60 min uptake ratio: 10.3). These results indicate that [(18)F]1 has in vivo kinetics comparable to PET radiopharmaceuticals currently under commercial development, demonstrating that [(18)F]1 is a desirable PET radioligand for Aβ plaque imaging.
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-ku, Seoul 135-710, Korea.
authors.forename: Iljung
authors.initials: I
authors.lastname: Lee
authors.forename: Yearn Seong
authors.initials: YS
authors.lastname: Choe
authors.forename: Joon Young
authors.initials: JY
authors.lastname: Choi
authors.forename: Kyung-Han
authors.initials: KH
authors.lastname: Lee
authors.forename: Byung-Tae
authors.initials: BT
authors.lastname: Kim
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D005462:Fluorine Radioisotopes; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010446:Peptide Fragments / Q000378:metabolism; D058225:Plaque, Amyloid / Q000378:metabolism*; D011869:Radioligand Assay; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D000077185:Resveratrol; D013237:Stereoisomerism; D013267:Stilbenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship; D013343:Styrenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: C571188:1-(2-fluoroethyl)-4-(4-N,N-dimethylaminostyryl)-1H-1,2,3-triazole; C571189:1-(4-(3-fluoropropoxy)styryl)-3,5-dimethoxybenzene; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D005462:Fluorine Radioisotopes; D010446:Peptide Fragments; D019275:Radiopharmaceuticals; D013267:Stilbenes; D013343:Styrenes; D014230:Triazoles; C075222:amyloid beta-protein (1-42); D000077185:Resveratrol