Synthesis and Ex Vivo Autoradiographic Evaluation of Ethyl-[beta]-d-galactopyranosyl-(1,4')-2'-deoxy-2'-[^sup 18^F]fluoro-[beta]-d-glucopyranoside--A Novel Radioligand for Lactose-Binding Protein: Implications for Early Detection of Pancreatic Carcinomas with PET

• Published in: Molecular imaging and biology Vol. 13; no. 3; p. 536
• Main Authors: Ying, Yunming, Ghosh, Pradip, Guo, Liwei, Pal, Ashutosh, Mukhapadhyay, Uday, Peng, Zhenghong, Yeh, Hsin Hsien, Bertolini, Susanna, Flores, Leo Garcia, Young, Daniel, Volgin, Andrei, Soghomonyan, Suren, Bornmann, William, Logsdon, Craig, Alauddin, Mian M, Gelovani, Juri G
• Format: Journal Article
• Language: English
• Published: New York Springer Nature B.V 01.06.2011
• ISSN: 1536-1632; 1860-2002
• DOI: 10.1007/s11307-010-0334-9

Previous studies demonstrated that the lactose-binding protein (hepatocellular carcinoma-intestine-pancreas and pancreatitis-associated proteins (HIP/PAP)) is upregulated >130 times in peritumoral pancreatic tissue as compared to normal pancreatic tissue. Therefore, we developed a new radiolabeled ligand of HIP/PAP, the ethyl-β-d-galactopyranosyl-(1,4')-2'-deoxy-2'-[^sup 18^F]fluoro-β-d-glucopyranoside (Et-[^sup 18^F]FDL) for noninvasive imaging of pancreatic carcinoma using positron emission tomography and computerized tomography (PET/CT). The novel precursor and radiolabeling methods for synthesis of Et-[^sup 18^F]FDL produced no isomers; the average decay-corrected radiochemical yield was 68%, radiochemical purity >99%, and specific activity >74 GBq/µmol. The radioligand properties of Et-[^sup 18^F]FDL were evaluated using an ex vivo autoradiography and immunohistochemistry in pancreatic tissue sections obtained from mice-bearing orthotopic pancreatic tumor xenografts. Et-[^sup 18^F]FDL binding to peritumoral pancreatic tissue sections strongly correlated with HIP/PAP expression (r=0.81) and could be completely blocked by treatment with 1 mM lactose. These results suggest that Et-[^sup 18^F]FDL is a promising agent which should be evaluated for detection of early pancreatic carcinomas by PET/CT imaging.[PUBLICATION ABSTRACT]