Molecular Imaging and Biology

, Volume 13, Issue 5, pp 812–818

Synthesis of 2′-Deoxy-2′-[18F]Fluoro-9-β-D-Arabinofuranosylguanine: a Novel Agent for Imaging T-Cell Activation with PET

  • Mohammad Namavari
  • Ya-Fang Chang
  • Brenda Kusler
  • Shahriar Yaghoubi
  • Beverly S. Mitchell
  • Sanjiv Sam Gambhir
Brief Article

DOI: 10.1007/s11307-010-0414-x

Cite this article as:
Namavari, M., Chang, Y., Kusler, B. et al. Mol Imaging Biol (2011) 13: 812. doi:10.1007/s11307-010-0414-x

Abstract

Purpose

9-(β-D-Arabinofuranosyl)guanine (AraG) is a guanosine analog that has a proven efficacy in the treatment of T-cell lymphoblastic disease. To test the possibility of using a radiofluorinated AraG as an imaging agent, we have synthesized 2′-deoxy-2′-[18F]fluoro-9-β-D-arabinofuranosylguanine ([18F]F-AraG) and investigated its uptake in T cells.

Procedure

We have synthesized [18F]F-AraG via a direct fluorination of 2-N-acetyl-6-O-((4-nitrophenyl)ethyl)-9-(3′,5′-di-O-trityl-2′-O-trifyl-β-D-ribofuranosyl)guanine with [18F]KF/K.2.2.2 in DMSO at 85°C for 45 min. [18F]F-AraG uptake in both a CCRF-CEM leukemia cell line (unactivated) and activated primary thymocytes was evaluated.

Results

We have successfully prepared [18F]F-AraG in 7–10% radiochemical yield (decay corrected) with a specific activity of 0.8–1.3 Ci/μmol. Preliminary cell uptake experiments showed that both a CCRF-CEM leukemia cell line and activated primary thymocytes take up the [18F]F-AraG.

Conclusion

For the first time to the best of our knowledge, [18F]F-AraG has been successfully synthesized by direct fluorination of an appropriate precursor of a guanosine nucleoside. This approach maybe also useful for the synthesis of other important positron emission tomography (PET) probes such as [18F]FEAU, [18F]FMAU, and [18F]FBAU which are currently synthesized by multiple steps and involve lengthy purification. The cell uptake studies support future studies to investigate the use of [18F]F-AraG as a PET imaging agent of T cells.

Key words

ImagingT cells9-(β-D-Arabinofuranosyl) guanine (AraG)Positron emission tomography (PET)

Copyright information

© Academy of Molecular Imaging and Society for Molecular Imaging 2010

Authors and Affiliations

  • Mohammad Namavari
    • 1
    • 2
    • 3
  • Ya-Fang Chang
    • 1
    • 2
    • 3
  • Brenda Kusler
    • 4
    • 5
  • Shahriar Yaghoubi
    • 1
    • 2
    • 3
  • Beverly S. Mitchell
    • 4
    • 5
  • Sanjiv Sam Gambhir
    • 1
    • 2
    • 3
  1. 1.Molecular Imaging Program at Stanford (MIPS)Stanford UniversityStanfordUSA
  2. 2.Department of Radiology, Bio-X ProgramStanford UniversityStanfordUSA
  3. 3.Department of Bioengineering, Bio-X ProgramStanford UniversityStanfordUSA
  4. 4.Division of Oncology, Stanford Cancer CenterStanford UniversityStanfordUSA
  5. 5.Division of Hematology, Stanford Cancer CenterStanford UniversityStanfordUSA