Synthesis and ex vivo autoradiographic evaluation of ethyl-β-D-galactopyranosyl-(1,4')-2'-deoxy-2'-[18F]fluoro-β-D-glucopyranoside--a novel radioligand for lactose-binding protein: implications for early detection of pancreatic carcinomas with PET.
BACKGROUND
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'-[¹⁸F]fluoro-β-D-glucopyranoside (Et-[¹⁸F]FDL) for noninvasive imaging of pancreatic carcinoma using positron emission tomography and computerized tomography (PET/CT).


METHODS
The novel precursor and radiolabeling methods for synthesis of Et-[¹⁸F]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-[¹⁸F]FDL were evaluated using an ex vivo autoradiography and immunohistochemistry in pancreatic tissue sections obtained from mice-bearing orthotopic pancreatic tumor xenografts.


CONCLUSIONS
Et-[¹⁸F]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.


CONCLUSIONS
These results suggest that Et-[¹⁸F]FDL is a promising agent which should be evaluated for detection of early pancreatic carcinomas by PET/CT imaging.
Ying
Yunming
Y
Department of Experimental Diagnostic Imaging, Center for Advanced Biomedical Imaging Research (CABIR), The University of Texas MD Anderson Cancer Center, 1881 East Road, 3SCR2.3924, Houston, TX, 77030, USA.
Ghosh
Pradip
P
Department of Experimental Diagnostic Imaging, Center for Advanced Biomedical Imaging Research (CABIR), The University of Texas MD Anderson Cancer Center, 1881 East Road, 3SCR2.3924, Houston, TX, 77030, USA.
Guo
Liwei
L
Department of Experimental Diagnostic Imaging, Center for Advanced Biomedical Imaging Research (CABIR), The University of Texas MD Anderson Cancer Center, 1881 East Road, 3SCR2.3924, Houston, TX, 77030, USA.
Pal
Ashutosh
A
Department of Experimental Diagnostic Imaging, Center for Advanced Biomedical Imaging Research (CABIR), The University of Texas MD Anderson Cancer Center, 1881 East Road, 3SCR2.3924, Houston, TX, 77030, USA.
Mukhapadhyay
Uday
U
Department of Experimental Diagnostic Imaging, Center for Advanced Biomedical Imaging Research (CABIR), The University of Texas MD Anderson Cancer Center, 1881 East Road, 3SCR2.3924, Houston, TX, 77030, USA.
Peng
Zhenghong
Z
Department of Experimental Diagnostic Imaging, Center for Advanced Biomedical Imaging Research (CABIR), The University of Texas MD Anderson Cancer Center, 1881 East Road, 3SCR2.3924, Houston, TX, 77030, USA.
Yeh
Hsin Hsien
HH
Department of Experimental Diagnostic Imaging, Center for Advanced Biomedical Imaging Research (CABIR), The University of Texas MD Anderson Cancer Center, 1881 East Road, 3SCR2.3924, Houston, TX, 77030, USA.
Bertolini
Susanna
S
Department of Experimental Diagnostic Imaging, Center for Advanced Biomedical Imaging Research (CABIR), The University of Texas MD Anderson Cancer Center, 1881 East Road, 3SCR2.3924, Houston, TX, 77030, USA.
Flores
Leo Garcia
LG
Department of Experimental Diagnostic Imaging, Center for Advanced Biomedical Imaging Research (CABIR), The University of Texas MD Anderson Cancer Center, 1881 East Road, 3SCR2.3924, Houston, TX, 77030, USA.
Young
Daniel
D
Department of Experimental Diagnostic Imaging, Center for Advanced Biomedical Imaging Research (CABIR), The University of Texas MD Anderson Cancer Center, 1881 East Road, 3SCR2.3924, Houston, TX, 77030, USA.
Volgin
Andrei
A
Department of Experimental Diagnostic Imaging, Center for Advanced Biomedical Imaging Research (CABIR), The University of Texas MD Anderson Cancer Center, 1881 East Road, 3SCR2.3924, Houston, TX, 77030, USA.
Soghomonyan
Suren
S
Department of Experimental Diagnostic Imaging, Center for Advanced Biomedical Imaging Research (CABIR), The University of Texas MD Anderson Cancer Center, 1881 East Road, 3SCR2.3924, Houston, TX, 77030, USA.
Bornmann
William
W
Department of Experimental Diagnostic Imaging, Center for Advanced Biomedical Imaging Research (CABIR), The University of Texas MD Anderson Cancer Center, 1881 East Road, 3SCR2.3924, Houston, TX, 77030, USA.
Logsdon
Craig
C
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Alauddin
Mian M
MM
Department of Experimental Diagnostic Imaging, Center for Advanced Biomedical Imaging Research (CABIR), The University of Texas MD Anderson Cancer Center, 1881 East Road, 3SCR2.3924, Houston, TX, 77030, USA.
Gelovani
Juri G
JG
Department of Experimental Diagnostic Imaging, Center for Advanced Biomedical Imaging Research (CABIR), The University of Texas MD Anderson Cancer Center, 1881 East Road, 3SCR2.3924, Houston, TX, 77030, USA. jgelovani@mdanderson.org.
D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D001345:Autoradiography / Q000379:methods*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004187:Disaccharides / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D055088:Early Detection of Cancer; D005960:Glucosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D054879:Halogenation; D007150:Immunohistochemistry; D007785:Lactose / Q000378:metabolism*; D037181:Lectins, C-Type / Q000378:metabolism; D008024:Ligands; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging*; D000073718:Pancreatitis-Associated Proteins; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004187:Disaccharides; D005960:Glucosides; D037181:Lectins, C-Type; D008024:Ligands; D009363:Neoplasm Proteins; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; D019275:Radiopharmaceuticals; C560565:ethyl galactopyranosyl-(1-4)-2'-deoxy-2'-fluoroglucopyranoside; D007785:Lactose