N3-Substituted Thymidine Analogues: Radiosyntheses of N3-[4-(4-(2-[18F] fluoroethyl)phenyl)butyl]thymidine and N3-[5-(4-(2-[18F]fluoroethyl)- phenyl)pentyl]thymidine for PET

Radiosyntheses of two new N3-substituted analogues of thymidine, N3-[4-(4-(2-[18F]fluoroethyl)phenyl)butyl] thymidine ([18F]-FEPBT) and N3-[5-(4-(2-[18F]fluoroethyl)phenyl)pentyl]thymidine ([18F]-FEPPT) are reported. Synthesesof the precursor compounds, 3',5'-O-bis-tetrahydropyranyl-N3-[4-(4-(2-methanesulfonyl-ethyl)phenyl)butyl]thymidine and 3',5'-O-bis-tetrahydropyranyl-N3-[5-(4-(2-methanesulfonyl-ethyl)phenyl)pentyl]thymidine are described. Radiofluorination of these precursors was performed using K[18F]/kryptofix 2.2.2. in dry MeCN. Hydrolysis of the protecting groups followed by HPLC purification yielded the desired products [18F]-FEPBT and [18F]-FEPPT. The radiochemical yields of [18F]-FEPBT were 35%-48% decay corrected (d. c.) with an average of 44%; and those of [18F]-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/μmol at the end of synthesis. The synthesis time was 80-90 min from the end of bombardment (EOB).