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

Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, CA 94305, USA.
Molecular imaging and biology: MIB: the official publication of the Academy of Molecular Imaging (Impact Factor: 2.77). 10/2011; 13(5):812-8. DOI: 10.1007/s11307-010-0414-x
Source: PubMed


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'-[(18)F]fluoro-9-β-D-arabinofuranosylguanine ([(18)F]F-AraG) and investigated its uptake in T cells.
We have synthesized [(18)F]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 [(18)F]KF/K.2.2.2 in DMSO at 85°C for 45 min. [(18)F]F-AraG uptake in both a CCRF-CEM leukemia cell line (unactivated) and activated primary thymocytes was evaluated.
We have successfully prepared [(18)F]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 [(18)F]F-AraG.
For the first time to the best of our knowledge, [(18)F]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 [(18)F]FEAU, [(18)F]FMAU, and [(18)F]FBAU which are currently synthesized by multiple steps and involve lengthy purification. The cell uptake studies support future studies to investigate the use of [(18)F]F-AraG as a PET imaging agent of T cells.

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    • "One such PET probe, [(18)F]FAC (1-[2'-deoxy-2'-[(18)F]fluoroarabinofura­nosyl] cytosine), was used to visualize lymphoid organs and localized activation of anti-tumor T cell responses 61. The development of other probes which may selectively image immune activation are currently underway 62. "
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