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

被引:8
作者
Turkman, Nashaat [1 ]
Pal, Ashutosh [1 ]
Tong, William P. [1 ]
Gelovani, Juri G. [1 ]
Alauddin, Mian M. [1 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Dept Expt Diagnost Imaging, CABIR, Houston, TX 77030 USA
关键词
fluorine-18; lactose; HIP/PAP; pancreatic carcinoma; PET; PRIMARY LIVER-CANCER; BINDING PROTEIN; GENE; EXPRESSION; HIP/PAP; INTESTINE; ALPHA;
D O I
10.1002/jlcr.1855
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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-beta-D-galactopyranosyl-(1,4')-2'-deoxy-2'-[F-18]fluoro-beta-D-glucopyranoside (Et-[F-18]-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'-[F-18]fluoroethyl-beta-D-lactose for PET imaging of pancreatic carcinomas. Methods: Two precursor compounds, 1'-bromoethyl-2',3',6',2,3,4,6-hepta-O-acetyl-beta-D-lactose 4, and 1'-p-toluenesulfonylethyl-2',3',6',2,3,4,6-hepta-O-acetyl-beta-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'-[F-18]fluoroethyl-2',3',6',2,3,4,6-hepta-O-acetyl-beta-D-lactose ([F-18]-6) purified by HPLC. After hydrolysis of the protecting groups, the 1'-[F-18]fluoroethyl-beta-D-lactose [F-18]-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/mu mol. Conclusion: A new analog of lactose, 1'-[F-18]fluoroethyl-beta-D-lactose, has been synthesized in good yields, with high purity and high specific activity suitable for PET imaging of early pancreatic carcinomas.
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页码:233 / 238
页数:6
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