Synthesis and preliminary evaluation of 9-(4-[¹⁸F]-fluoro-3- hydroxymethylbutyl)guanine ([¹⁸F]FHBG): A new potential imaging agent for viral infection and gene therapy using PET

Synthesis and preliminary biological evaluation of 9-(4-[¹⁸F]-fluoro- 3-hydroxymethylbutyl)-guanine ([¹⁸F]FHBG) is reported. 9-(4-Hydroxy-3- hydroxymethylbutyl)-guanine (penciclovir) 4 was converted to 9-[N², O-bis- (methoxytrityl)-3-(tosylmethybutyl)]guanine 7 by treatment with methoxytrityl chloride followed by tosylation. The tosylate 7 was reacted with either tetrabutylammonium fluoride or KF in the presence of kryptofix 2.2.2. to produce the 4-fluoro-N²-O-bis-(methoxytrityl) derivative 8. Removal of the methoxytrityl groups by acidic hydrolysis produced FHBG 5. Radiolabeled product [¹⁸F]FHBG was prepared by fluorination of the tosylate 7 with [¹⁸F]KF and kryptofix 2.2.2. The labeled product was isolated by HPLC purification on a reverse-phase C₁₈ column, and eluted at 12 min with 15% acetonitrile in water at a flow rate of 2.25 mL/min. Radiochemical yield was 8.0-22.3% with an average of 12% in 7 runs (corrected for decay). Synthesis time was 90 to 100 min including HPLC purification with radiochemical purity >99%, and average specific activity of 320 mCi/μmol. In vitro studies of the compound in HT-29 colon cancer cells revealed 18.2-fold higher uptake into transduced cells compared to control in 3 h. The agent may be useful for imaging viral infection or transfected cells in gene therapy.