Synthesis of 2'-deoxy-2'-[18F]fluoro-9-β-D-arabinofuranosylguanine: a novel agent for imaging T-cell activation with PET.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Namavari
Mohammad
M
Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, CA 94305, USA.
Chang
Ya-Fang
YF
Kusler
Brenda
B
Yaghoubi
Shahriar
S
Mitchell
Beverly S
BS
Gambhir
Sanjiv Sam
SS
D001087:Arabinonucleosides / Q000138:chemical synthesis*; D045744:Cell Line, Tumor; D006801:Humans; D008213:Lymphocyte Activation; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D049268:Positron-Emission Tomography; D013601:T-Lymphocytes / Q000276:immunology*
D001087:Arabinonucleosides; C028771:9-arabinofuranosylguanine