title: Preliminary evaluation of 1'-[(18)F]fluoroethyl-β-D-lactose ([(18)F]FEL) for detection of pancreatic cancer in nude mouse orthotopic xenografts.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  [(18)F]FEL may be useful for non-invasive imaging of early-stage pancreatic tumours by PET. The results warrant further studies.
authors.affiliation: Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Thiruvengadam
authors.initials: T
authors.lastname: Arumugam
authors.affiliation: Center for Advanced Biomedical Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Paolillo
authors.affiliation: Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Young
authors.affiliation: Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: XiaoXia
authors.initials: X
authors.lastname: Wen
authors.affiliation: Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Craig D
authors.initials: CD
authors.lastname: Logsdon
authors.affiliation: Center for Advanced Biomedical Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Louis
authors.initials: L
authors.lastname: De Palatis
authors.affiliation: Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: alauddin@mdanderson.org.
authors.forename: Mian M
authors.initials: MM
authors.lastname: Alauddin
mesh_terms: D000818:Animals; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D006801:Humans; D007124:Immunoenzyme Techniques; D007785:Lactose / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D008163:Luminescent Measurements; D008279:Magnetic Resonance Imaging; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D000073718:Pancreatitis-Associated Proteins; D049268:Positron-Emission Tomography; D011506:Proteins / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: C000592777:1'-fluoroethyllactose; D005462:Fluorine Radioisotopes; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins; C000612141:REG3A protein, human; D019275:Radiopharmaceuticals; C490253:Reg3b protein, mouse; D007785:Lactose
keywords: HIP/PAP; PET; Pancreatic cancer; Tumour imaging; [(18)F]lactose