SYNTHESIS AND PRELIMINARY EVALUATION OF 9-(4-[F-18]-FLUORO-3-HYDROXYMETHYLBUTYL)GUANINE ([F-18]FHBG) - A NEW POTENTIAL IMAGING AGENT FOR VIRAL-INFECTION AND GENE-THERAPY USING PET

Synthesis and preliminary biological evaluation of 9-(4-[F-18]-fluoro- 3-hydroxymethylbutyl)-guanine ([F-18]FHBG) is reported. 9-(4-Hydroxy-3 -hydroxymethylbutyl)-guanine (penciclovir) 4 was converted to 9-[N-2, O-bis-(methoxytrityl)-3-(tosylmethybutyl)]guanine 7 by treatment with methoxytrityl chloride followed by tosylation. The tosylate 7 was reac ted with either tetrabutylammonium fluoride or KF in the presence of k ryptofix 2.2.2. to produce the 4-fluoro-N-2-O-bis-(methoxytrityl) deri vative 8. Removal of the methoxytrityl groups by acidic hydrolysis pro duced FHBG 5. Radiolabeled product [F-18]FHBG was prepared by fluorina tion of the tosylate 7 with [F-18]KF and kryptofix 2.2.2. The labeled product was isolated by HPLC purification on a reverse phase C-18 colu mn, 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 avera ge specific activity of 320 mCi/mu mol. In vitro studies of the compou nd in HT-29 colon cancer cells revealed 18.2-fold higher uptake into t ransduced cells compared to control in 3 h. The agent may be useful fo r imaging viral infection or transfected cells in gene therapy. (C) 19 98 Elsevier Science Inc.