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

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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.

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Acknowledgements

This work was supported in part by NCI In Vivo Cellular Molecular Imaging Center grant P50 CA114747 (SSG). We also thank Dr. David Dick for the [18F] production, Dr. Frederick T. Chin for modification of a GE TRACERlab FX-FN synthetic module for radiosynthesis, and Dr. Jelena Levi for her review of the manuscript.

Conflict of interest disclosure

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Molecular Imaging Program at Stanford (MIPS), Stanford University, 318 Campus Dr., Clark Center, E-150, Stanford, CA, 94305, USA

    Mohammad Namavari, Ya-Fang Chang, Shahriar Yaghoubi & Sanjiv Sam Gambhir

  2. Department of Radiology, Bio-X Program, Stanford University, 318 Campus Dr., Clark Center, E-150, Stanford, CA, 94305, USA

    Mohammad Namavari, Ya-Fang Chang, Shahriar Yaghoubi & Sanjiv Sam Gambhir

  3. Department of Bioengineering, Bio-X Program, Stanford University, 318 Campus Dr., Clark Center, E-150, Stanford, CA, 94305, USA

    Mohammad Namavari, Ya-Fang Chang, Shahriar Yaghoubi & Sanjiv Sam Gambhir

  4. Division of Oncology, Stanford Cancer Center, Stanford University, Stanford, CA, USA

    Brenda Kusler & Beverly S. Mitchell

  5. Division of Hematology, Stanford Cancer Center, Stanford University, Stanford, CA, USA

    Brenda Kusler & Beverly S. Mitchell

Authors
  1. Mohammad Namavari
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  2. Ya-Fang Chang
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  3. Brenda Kusler
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  4. Shahriar Yaghoubi
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  6. Sanjiv Sam Gambhir
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Correspondence to Sanjiv Sam Gambhir.

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Namavari, M., Chang, YF., Kusler, B. et al. Synthesis of 2′-Deoxy-2′-[18F]Fluoro-9-β-D-Arabinofuranosylguanine: a Novel Agent for Imaging T-Cell Activation with PET. Mol Imaging Biol 13, 812–818 (2011). https://doi.org/10.1007/s11307-010-0414-x

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