Abstract: In this study, four fluorine-substituted resveratrol derivatives were designed and synthesized as candidates for β-amyloid(Aβ) plaque imaging. The in vitro binding studies using Aβ_1-42peptide aggregates were carried out with the four resveratrol derivatives. The F-18 labeled derivatives with the highest binding affinities to Aβ_1-42 aggregates were prepared using the appropriate mesylate precursors in DMSO, and the stability and partition coefficient were also evaluated. And the biodistribution studies were performed using the normal Kunming mice. Among all derivatives examined, (E)-1-(3, 5-dimethoxystyryl)-4-(2-(2-(2-fluoroethoxy)ethoxyethoxy)-benzene (Compound 7) shows highest binding affinity to Aβ_1-42 peptide aggregates (K_i=43.76 nmol/L, with ［¹²⁵I］IMPY as radioligand). No-carrier-added ［¹⁸F］F-7 was successfully prepared within 32 min (uncorrected yield （23±2）%) and purified using a Sep Pak C18 cartridge with a high radiochemical purity (>95%). ［¹⁸F］ F-7 shows a good stability in saline and an adequate lipophilicity (lg P=3.08). For biodistribution, ［¹⁸F］F-7 displays moderate initial brain uptake (（0.55±0.05）%ID/g at 2 min ) with rapid wash-out from brains (（0.06±0.01）%ID/g at 60 min); 2-to-60 min uptake ratio is 9. Of these compounds, ［¹⁹F］ F-7 shows the highest binding affinity, and ［¹⁸F］ F-7 exhibits suitable lipophilicity and reasonable initial brain uptake and fast washout. All these results indicate that ［¹⁸F］ F-7 is a suitable radioligand for Aβ plaque imaging.