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

Radiosyntheses of two new N-3-substituted analogues of thymidine, N-3-[4-(4-(2-[F-18]fluoroethyl)phenyl)butyl] thymidine ([F-18]-FEPBT) and N-3-[5-(4-(2-[F-18]fluoroethyl)phenyl)pentyl]thymidine ([F-18]-FEPPT) are reported. Synthesesof the precursor compounds, 3',5'-O-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. Radiofluorination of these precursors was performed using K[F-18]/kryptofix 2.2.2. in dry MeCN. Hydrolysis of the protecting groups followed by HPLC purification yielded the desired products [F-18]-FEPBT and [F-18]-FEPPT. The radiochemical yields of [F-18]-FEPBT were 35%-48% decay corrected (d. c.) with an average of 44%; and those of [F-18]-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/mu mol at the end of synthesis. The synthesis time was 80-90 min from the end of bombardment (EOB).