Synthesis of [¹⁸F]‐labeled 2′‐deoxy‐2′‐fluoro‐5‐methyl‐1‐β‐D‐arabinofuranosyluracil ([¹⁸F]‐FMAU)

Abstract

SummarySynthesis of 2 0 -deoxy-2 0 -[ 1-bromo-derivative 3 and coupled with protected thymine 4. The crude product mixture (5a and 5b) was hydrolyzed in base and purified by HPLC to obtain the radiolabeled FMAU 6a. The radiochemical yield of 6a was 20-30% decay corrected (d.c.) in four steps with an average of 25% in four runs. Radiochemical purity was >99% and average specific activity was 2300 mCi/mmol at the end of synthesis (EOS). The synthesis time was 3.5-4.0 h from the end of bombardment (EOB).

Semiautomated Radiosynthesis and Biological Evaluation of [18F]FEAU: A Novel PET Imaging Agent for HSV1-tk/sr39tk Reporter Gene Expression

“…The reference standards for the 1 [18F]-3b (33±8%; n=4) was eluted off the cartridge with ethyl acetate (3 mL) into a 5-mL conical vial and used directly in the next step. Product identity (t R =9.6 min) was confirmed by using analytical HPLC Method A [16,18]. 2-deoxy-2-[ 18 F]fluoro-3,5-di-O-benzoyl-α-D- F]-3b residue.…”

“…An additional evaporation cycle with toluene (1 mL) was also completed. After product identity (t R = 8.0 min) was confirmed, the [ 18 F]-4 residue (85±8%; n=4) was used directly in the coupling step [16]. 1-(3′,5′-di-O-benzoyl-2′-deoxy-2′-[ 18 F]fluoro-β-Darabinofuranose)-5-ethyluracil 7b and 7b′-Dichloroethane (0.5 mL) was added to the crude 2,4-bis-O-(trimethylsilyl)-5-ethyluracil 6 from the Method B, and the entire mixture was transferred to the conical vial containing the dried [ 18 F]-4b residue.…”

“…The remaining mixture was loaded onto a silica gel Sep-pak plus cartridge, and the cartridge was eluted with 10% methanol in dichloromethane (3 mL). After coupled products were confirmed (α-anomer: t R =4.4 min; β-anomer: t R = 4.8 min) by standard coinjection, the anomeric [ 18 F]-7 mixture (83 ±6%; n=4) was not separated and used directly in the final deprotection step [16]. [16].…”

“…After coupled products were confirmed (α-anomer: t R =4.4 min; β-anomer: t R = 4.8 min) by standard coinjection, the anomeric [ 18 F]-7 mixture (83 ±6%; n=4) was not separated and used directly in the final deprotection step [16]. [16]. The organic solvents were evaporated from the [ 18 F]-7 mixture via heating at 45°C and helium flow.…”

“…We [8] and other groups [9,15] have recently reported that radiolabeled FEAU, a 5-ethyl-substituted derivative of [ 18 F]FMAU, demonstrates high sensitivity and selectivity to both HSV1-tk and HSV1-sr39tk in cell uptake studies. Unlike [ 18 F]FMAU [16] that binds mainly to mammalian tk and is used as a marker for cell proliferation, [ 18 …”