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

Nucl Med Biol. 1998 Apr;25(3):175-80. doi: 10.1016/s0969-8051(97)00160-1.


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.

MeSH terms

  • Acyclovir / analogs & derivatives
  • Antiviral Agents
  • Biological Transport
  • Colonic Neoplasms
  • Fluorine Radioisotopes* / pharmacokinetics
  • Genetic Therapy
  • Guanine / analogs & derivatives*
  • Guanine / chemical synthesis
  • Guanine / pharmacokinetics
  • Humans
  • Indicators and Reagents
  • Molecular Structure
  • Radionuclide Imaging
  • Tumor Cells, Cultured
  • Virus Diseases / diagnostic imaging


  • 9-(4-fluoro-3-hydroxymethylbutyl)guanine
  • Antiviral Agents
  • Fluorine Radioisotopes
  • Indicators and Reagents
  • penciclovir
  • Guanine
  • Acyclovir