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

Abstract 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′‐[ 18 F]fluoro‐ β ‐ D ‐glucopyranoside (Et‐[ 18 F]‐FDL), a radiofluorinated lactose analog for positron emission tomography (PET) of small pancreatic carcinomas in mice. However, synthesis of the precursor for Et‐[ 18 F]‐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′‐[ 18 F]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′‐[ 18 F]fluoroethyl‐2′,3′,6′,2,3,4,6‐hepta‐ O ‐acetyl‐ β ‐ D ‐lactose ([ 18 F]‐6) purified by HPLC. After hydrolysis of the protecting groups, the 1′‐[ 18 F]fluoroethyl‐ β ‐ D ‐lactose [ 18 F]‐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/ µ mol. Conclusion : A new analog of lactose, 1′‐[ 18 F]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. Copyright © 2011 John Wiley & Sons, Ltd.