Radiosynthesis of 1′-[¹⁸F]fluoroethyl-β-D-lactose ([¹⁸F]-FEL) for early detection of pancreatic carcinomas with PET

Introduction: The hepatocellular carcinoma-intestine-pancreas and pancreatitis-associated proteins, also known as lactose-binding protein, is upregulated in peritumoral pancreatic tissue. Previously, we reported ethyl-β-D-galactopyranosyl-(1,4′)-2′-deoxy-2′-[ ¹⁸F]fluoro-β-D-glucopyranoside (Et-[¹⁸F]-FDL), a radiofluorinated lactose analog for positron emission tomography (PET) of small pancreatic carcinomas in mice. However, synthesis of the precursor for Et-[ ¹⁸F]-FDL involves 11 steps, which is quite lengthy, and produces overall low yields. Here, we report on synthesis and radiolabeling of another analog of lactose, the 1′-[¹⁸F]fluoroethyl-β-D-lactose for PET imaging of pancreatic carcinomas. Methods: Two precursor compounds, 1′-bromoethyl-2′,3′,6′,2,3,4,6-hepta-O-acetyl-β-D- lactose 4, and 1′-p-toluenesulfonylethyl-2′,3′,6′,2,3,4, 6-hepta-O-acetyl-β-D-lactose 5, were synthesized in two and three steps, respectively; then, cold fluorination and radiofluorination of these precursors were performed. The reaction mixture was passed through a silica gel Sep-pack cartridge, eluted with EtOAc, and the 1′-[¹⁸F]fluoroethyl- 2′,3′,6′,2,3,4,6-hepta-O-acetyl-β-D-lactose ([ ¹⁸F]-6) purified by HPLC. After hydrolysis of the protecting groups, the 1′-[¹⁸F]fluoroethyl-β-D-lactose [¹⁸F]-7 was neutralized, diluted with saline, filtered through a sterile Millipore filter, and analyzed by radio-TLC. Results: The average decay-corrected radiochemical yield was 9% (n = 7) with>99% radiochemical purity and specific activity of 55.5 GBq/μmol. Conclusion: A new analog of lactose, 1′-[ ¹⁸F]fluoroethyl-β-D-lactose, has been synthesized in good yields, with high purity and high specific activity suitable for PET imaging of early pancreatic carcinomas.