title: 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.
abstract: 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/micromol. 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.
authors.affiliation: PET Imaging Science Center, University of Southern California, School of Medicine, Los Angeles 90033, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Alauddin
authors.forename: P S
authors.initials: PS
authors.lastname: Conti
mesh_terms: D000212:Acyclovir / Q000031:analogs & derivatives; D000998:Antiviral Agents; D001692:Biological Transport; D003110:Colonic Neoplasms; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D015316:Genetic Therapy; D006147:Guanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D006801:Humans; D007202:Indicators and Reagents; D015394:Molecular Structure; D011877:Radionuclide Imaging; D014407:Tumor Cells, Cultured; D014777:Virus Diseases / Q000000981:diagnostic imaging
chemical_list: C113308:9-(4-fluoro-3-hydroxymethylbutyl)guanine; D000998:Antiviral Agents; D005462:Fluorine Radioisotopes; D007202:Indicators and Reagents; C053539:penciclovir; D006147:Guanine; D000212:Acyclovir