N~3-Substituted Thymidine Analogues: Radiosyntheses of N~3-(4-(4-(2-(~(18)F) fluoroethyl)phenyl)butyl)thymidine and N~3-(5-(4-(2-(~(18)F)fluoroethy)-phenyl)pentyl)thymidine for PET

摘要

Abstract: Radiosyntheses of two new N~3-substituted analogues of thymidine, N~3-[4-(4-(2-[~(I8)F]fluoroethyl)phenyl)butyl] thymidine ([~(18)F]-FEPBT) and N~3-[5-(4-(2-[~(18)F]fIuoroethyl)phenyl)pentyl]thymidine ([~(18)F]-FEPPT) are reported. Syntheses of the precursor compounds, 3 ',5 '-0-bis-tetrahydropyranyl-N~3-[4-(4-(2-methanesulfonyl-ethyl)phenyl)butyl]thymidine and 3',5'-O-bis-tetrahydropyranyl-N~3-[5-(4-(2-methanesulfonyl-ethyl)phenyl)pentyl]thymidine are described. Radiofluo-rination of these precursors was performed using K[~(l8)F]/kryptofix 2.2.2. in dry MeCN. Hydrolysis of the protecting groups followed by HPLC purification yielded the desired products [~(18)F]-FEPBT and [~(18)F]-FEPPT. The radiochemical yields of [~(18)F]-FEPBT were 35%-48% decay corrected (d. c.) with an average of 44%; and those of [~(18)F]-FEPPT were 32%-40% (d. c.) with an average of 37% in three runs per compound. Radiochemical purity was > 99% and specific activity was > 74 GBq/mumol at the end of synthesis. The synthesis time was 80-90 min from the end of bombardment (EOB).