Synthesis of 9-[(3-[¹⁸F]-fluoro-1-hydroxy-2-propoxy)methyl]guanine ([¹⁸F]-FHPG): A potential imaging agent of viral infection and gene therapy using PET

A no-carrier-added synthesis of 9-[(3-[¹⁸F]-fluoro-1-hydroxy-2-propoxy)methyl]guanine ([¹⁸F]-FHPG) is reported. The 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (DHPG) was converted to 9-[N²,O-bis(methoxytrityl)-3-(tosyl)-2-propoxy-methyl]guanine by treatment with methoxytrityl chloride followed by tosylation. The tosylate was reacted with [¹⁸F]-KF in the presence of kryptofix 2.2.2. to produce the 3-fluoro-N²-O-bis-(methoxytrityl) derivative. Removal of the methoxytrityl protecting groups by acid hydrolysis produced [¹⁸F]-FHPG. The labeled product was purified by HPLC on a reverse-phase C₁₈ column, and eluted in 9 min with a mobile phase of 5% acetonitrile in water. The radiochemical yield was 7-17%, with an average of 10% in 10 runs (corrected for decay to EOB). The radiochemical purity was > 99%, and specific activities with an average of 526 mCi/μmol were obtained. The synthesis time was 70-80 min, including HPLC purification and determination of radiochemical purity and specific activity.