Synthesis and evaluation of F-18 labeled 2 '-deoxy-2 '-fluoro-5-methyl-1-beta-L-arabinofuranosyluracil (L-[F-18]FMAU)

Abstract

L-[F-18]FMAU ([F-18]1b) was prepared from the precursor 2-O-[(trifluoromethyl)-sulfonyl]-1,3,5-tri-O-benzoyl-alpha-L-ribofuranose, by coupling the radioactive fluoro-sugar with the corresponding silylated thymine in 4 steps. The final products, including the alpha and beta anomer, 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 alpha/beta anomeric ratio of the compounds was about 1:9, and the radiochemical purity of the product (beta-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.