An improved synthesis of 1′-[¹⁸F]fluoroethyl-β- D -Lactose ([¹⁸F]-FEL) for positron emission tomography imaging of pancreatic cancer

Introduction Earlier, we reported syntheses of ethyl-β-d- galactopyranosyl-(1,4′)-2′-deoxy-2′-[¹⁸F]fluoro- β-d-glucopyranoside (Et-[¹⁸F]FDL) and 1′-[ ¹⁸F]fluoroethyl-β-d-lactose ([¹⁸F]-FEL) for positron emission tomography (PET) of pancreatic carcinoma. Et-[¹⁸F]FDL requires a precursor, which involves 11 steps to synthesize and produces overall low yields. Synthesis of precursors for [¹⁸F]-FEL requires four steps, but those precursors produced low radiochemical yields. Here, we report new precursors and an improved synthesis of [¹⁸F]-FEL. Method Two precursors, 1′-(methanesulfonyl)ethyl-2′,3′,6′,2,3,4,6- hepta-O-acetyl-β-d-lactose 2a and 1′-(p-nitrophenyl-sulfonyl)ethyl- 2′,3′,6′,2,3,4,6-hepta-O-acetyl-β-d-lactose 2b, were synthesized from lactose in four steps. Radiofluorination reactions were performed using K¹⁸F/kryptofix and the crude product [ ¹⁸F]-3 was purified by HPLC. Basic hydrolysis of [¹⁸F]-3 produced 1′-[¹⁸F]fluoroethyl-β-d-lactose [ ¹⁸F]-4, which was neutralized, diluted with saline, filtered on a 0.22-μm filter, and analyzed by radio-TLC. Results The average radiochemical yields of [¹⁸F]-4 (d. c.) from 2a and 2b were 21% (n = 6) and 65% (n = 6), respectively, with >99% radiochemical purity and specific activity of 55.5 GBq/μmol. Synthesis time was 90-95 min from the end of bombardment. Conclusion An improved synthesis of [¹⁸F]FEL has been achieved in high yields, with high purity and specific activity. Precursor 2b with this method should be applicable for high yield automated production in a commercial synthesis module for clinical application.