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

✍ Scribed by Nashaat Turkman; Ashutosh Pal; William P. Tong; Juri G. Gelovani; Mian M. Alauddin

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: French
• Weight: 266 KB
• Volume: 54
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.1855

✦ Synopsis

Introduction:

The hepatocellular carcinoma-intestine-pancreas and pancreatitis-associated proteins, also known as lactosebinding protein, is upregulated in peritumoral pancreatic tissue. Previously, we reported ethyl-b-D-galactopyranosyl-(1,4 0 )-2 0 -deoxy-2 0 -[ 18 F]fluoro-b-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 0 -[ 18 F]fluoroethyl-b-D-lactose for PET imaging of pancreatic carcinomas. Methods: Two precursor compounds, 1 0 -bromoethyl-2 0 ,3 0 ,6 0 ,2,3,4,6-hepta-O-acetyl-b-D-lactose 4, and 1 0 -p-toluenesulfonylethyl-2 0 ,3 0 ,6 0 ,2,3,4,6-hepta-O-acetyl-b-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 0 -[ 18 F]fluoroethyl-2 0 ,3 0 ,6 0 ,2,3,4,6-hepta-O-acetyl-b-D-lactose ([ 18 F]-6) purified by HPLC. After hydrolysis of the protecting groups, the 1 0 -[ 18 F]fluoroethyl-b-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) with499% radiochemical purity and specific activity of 55.5 GBq/lmol. Conclusion: A new analog of lactose, 1 0 -[ 18 F]fluoroethyl-b-D-lactose, has been synthesized in good yields, with high purity and high specific activity suitable for PET imaging of early pancreatic carcinomas.