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

9-(beta-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'-[F-18]fluoro-9-beta-D-arabinofuranosylguanine ([F-18]F-AraG) and investigated its uptake in T cells. We have synthesized [F-18]F-AraG via a direct fluorination of 2-N-acetyl-6-O-((4-nitrophenyl)ethyl)-9-(3',5'-di-O-trityl-2'-O-trifyl-beta-D-ribofuranosyl)guanine with [F-18]KF/K.2.2.2 in DMSO at 85A degrees C for 45 min. [F-18]F-AraG uptake in both a CCRF-CEM leukemia cell line (unactivated) and activated primary thymocytes was evaluated. We have successfully prepared [F-18]F-AraG in 7-10% radiochemical yield (decay corrected) with a specific activity of 0.8-1.3 Ci/mu mol. Preliminary cell uptake experiments showed that both a CCRF-CEM leukemia cell line and activated primary thymocytes take up the [F-18]F-AraG. For the first time to the best of our knowledge, [F-18]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 [F-18]FEAU, [F-18]FMAU, and [F-18]FBAU which are currently synthesized by multiple steps and involve lengthy purification. The cell uptake studies support future studies to investigate the use of [F-18]F-AraG as a PET imaging agent of T cells.