Introduction: Early detection of pancreatic cancer could save many thousands of lives. Non-invasive diagnostic imaging, including PET with [(18)F]FDG, has inadequate resolution for detection of small (2-3 mm) pancreatic tumours. We demonstrated the efficacy of PET imaging with an (18)F-labelled lactose derivative, [(18)F]FEDL, that targets HIP/PAP, a biomarker that is overexpressed in the peritumoural pancreas. We developed another analogue, 1-[(18)F]fluoroethyl lactose ([(18)F]FEL), which is simpler to synthesise, for the same application. We conducted a preliminary evaluation of the new probe and its efficacy in detecting orthotopic pancreatic carcinoma xenografts in mice.
Methods: Xenografts were developed in nude mice by injecting L3.6 pl/GL(+) pancreatic carcinoma cells into the pancreas of each mouse. Tumour growth was monitored by bioluminescence imaging (BLI); accuracy of BLI tumour size estimates was verified by MRI in two representative mice. When the tumour size reached approximately 2-3mm, the animals were injected with [(18)F]FEL (3.7 MBq) and underwent static PET/CT scans. Blood samples were collected at 2, 5, 10, 20 and 60 min after [(18)F]FEL injection to track blood clearance. Following imaging, animals were sacrificed and their organs and tumours/pancreatic tissue were collected and counted on a gamma counter. Pancreas, including tumour, was frozen, sliced and used for autoradiography and immunohistochemical analysis of HIP/PAP expression.
Results: Tumour growth was rapid, as observed by BLI and MRI. Blood clearance of [(18)F]FEL was bi-exponential, with half-lives of approximately 3.5 min and 40 min. Mean accumulation of [(18)F]FEL in the peritumoural pancreatic tissue was 1.29±0.295 %ID/g, and that in the normal pancreas of control animals was 0.090±0.101 %ID/g. [(18)F]FEL was cleared predominantly by the kidneys. Comparative analysis of autoradiographic images and immunostaining results demonstrated a correlation between [(18)F]FEL binding and HIP/PAP expression.
Conclusion: [(18)F]FEL may be useful for non-invasive imaging of early-stage pancreatic tumours by PET. The results warrant further studies.
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| http://dx.doi.org/10.1016/j.nucmedbio.2014.08.001 | DOI Listing |
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Preclinical PET imaging of HIP/PAP using 1'-F-fluoroethyl--D-lactose.
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Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100730, China.
Purpose: This study aims at preclinical evaluation of a recently reported lactose analogue, 1'-F-fluoroethyl--D-lactose (F-FEL), in binding to hepatocarcinoma-intestine-pancreas and pancreatitis-associated protein (HIP/PAP) and .
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Preliminary evaluation of 1'-[(18)F]fluoroethyl-β-D-lactose ([(18)F]FEL) for detection of pancreatic cancer in nude mouse orthotopic xenografts.
Nucl Med Biol
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Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address:
Introduction: Early detection of pancreatic cancer could save many thousands of lives. Non-invasive diagnostic imaging, including PET with [(18)F]FDG, has inadequate resolution for detection of small (2-3 mm) pancreatic tumours. We demonstrated the efficacy of PET imaging with an (18)F-labelled lactose derivative, [(18)F]FEDL, that targets HIP/PAP, a biomarker that is overexpressed in the peritumoural pancreas.
View Article and Find Full Text PDFOptimization of precursor synthesis, formulation and stability of 1'-[18F]fluoroethyl-β-D-lactose ([18F]FEL) for preclinical studies in detection of pancreatic cancer.
Nucl Med Biol
April 2014
Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address:
Introduction: 1'-[(18)F]Fluoroethyl-β-D-lactose ([(18)F]FEL) is a new PET imaging agent for early detection of pancreatic cancer and hepatocellular carcinoma. We previously reported the syntheses of [(18)F]FEL using a bromo- and a tosyl- precursor, followed by an improved method using a nosyl-precursor. However, some steps in the synthesis of the precursor appeared to be problematic producing low yields.
View Article and Find Full Text PDFAn improved synthesis of 1'-[18F]fluoroethyl-β-D-lactose ([18F]-FEL) for positron emission tomography imaging of pancreatic cancer.
J Labelled Comp Radiopharm
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Department of Experimental Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA; Wayne state University, Detroit, MI, USA.
Introduction: Earlier, we reported syntheses of ethyl-β-D-galactopyranosyl-(1,4')-2'-deoxy-2'-[(18)F]fluoro-β-D-glucopyranoside (Et-[(18)F]FDL) and 1'-[(18)F]fluoroethyl-β-D-lactose ([(18)F]-FEL) for positron emission tomography (PET) of pancreatic carcinoma. Et-[(18)F]FDL requires a precursor, which involves 11 steps to synthesize and produces overall low yields. Synthesis of precursors for [(18)F]-FEL requires four steps, but those precursors produced low radiochemical yields.
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