Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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Synthesis and Evaluation of F-18 Labeled 2'-Deoxy-2'-fluoro-5-methyl-1-β-L-arabinofuranosyluracil (L-[18F]FMAU)

  • Jo, Nam-Hyun (Biomaterial Chemistry Research Center, Korea Institute of Science and Technology) ;
  • Moon, Byung-Seok (Laboratory of Radiopharmaceuticals, Korea Institute of Radiological and Medical Sciences) ;
  • Hong, Su-Hee (Laboratory of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences) ;
  • An, Gwang-Il (Laboratory of Radiopharmaceuticals, Korea Institute of Radiological and Medical Sciences) ;
  • Choi, Tae-Hyun (Laboratory of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences) ;
  • Cheon, Gi-Jeong (Laboratory of Radiopharmaceuticals, Korea Institute of Radiological and Medical Sciences) ;
  • Cho, Jung-Hyuck (Biomaterial Chemistry Research Center, Korea Institute of Science and Technology) ;
  • Yoo, Kyung-Ho (Biomaterial Chemistry Research Center, Korea Institute of Science and Technology) ;
  • Lee, Kyo-Chul (Laboratory of Radiopharmaceuticals, Korea Institute of Radiological and Medical Sciences) ;
  • Oh, Chang-Hyun (Biomaterial Chemistry Research Center, Korea Institute of Science and Technology)
  • Published : 2007.12.20
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Abstract

L-[18F]FMAU ([18F]1b) was prepared from the precursor 2-O-[(trifluoromethyl)-sulfonyl]-1,3,5-tri-Obenzoyl- α-L-ribofuranose, by coupling the radioactive fluoro-sugar with the corresponding silylated thymine in 4 steps. The final products, including the α and β anomers, were purified using reverse phase HPLC with an appropriate solvent (5% CH3CN/H2O) at a flow rate of 3.0 mL/min. The total elapsed time of synthesis was about 180-200 min from EOB. The α/β anomeric ratio of the compounds was about 1:9, and the radiochemical purity of the product (β-form) was >98% with decay-corrected yields of 25-35%. All radioactive samples were confirmed using co-injection with pure non-radioactive analogues in every step. In the cellular uptake in vitro test of herpes simplex virus-thymidine kinase (HSV1-TK) gene expressed cells, the percent uptake of injected dose (%ID) of L- and D-FMAU was 37.28 and 65.86, respectively after 240 min incubation. However, the relative uptake (MCA-TK/MCA cellular uptake ratio) of L-FMAU was higher than that of D-FMAU (%ID of L-FMAU, 0.36 and D-FMAU, 0.93 after 240 min incubation in MCA cells). This means that L-FMAU will show better specific HSV1-TK gene expressed cell uptake for selective HSV1-TK gene imaging.

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References

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