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).