title: Detection of pancreatic carcinomas by imaging lactose-binding protein expression in peritumoral pancreas using [18F]fluoroethyl-deoxylactose PET/CT.
abstract: BACKGROUND
  Early diagnosis of pancreatic carcinoma with highly sensitive diagnostic imaging methods could save lives of many thousands of patients, because early detection increases resectability and survival rates. Current non-invasive diagnostic imaging techniques have inadequate resolution and sensitivity for detection of small size ( approximately 2-3 mm) early pancreatic carcinoma lesions. Therefore, we have assessed the efficacy of positron emission tomography and computer tomography (PET/CT) imaging with beta-O-D-galactopyranosyl-(1,4')-2'-deoxy-2'-[(18)F]fluoroethyl-D-glucopyranose ([(18)F]FEDL) for detection of less than 3 mm orthotopic xenografts of L3.6pl pancreatic carcinomas in mice. [(18)F]FEDL is a novel radioligand of hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP), which is overexpressed in peritumoral pancreatic acinar cells.
  
  
  RESULTS
  Dynamic PET/CT imaging demonstrated rapid accumulation of [(18)F]FEDL in peritumoral pancreatic tissue (4.04+/-2.06%ID/g), bi-exponential blood clearance with half-lives of 1.65+/-0.50 min and 14.14+/-3.60 min, and rapid elimination from other organs and tissues, predominantly by renal clearance. Using model-independent graphical analysis of dynamic PET data, the average distribution volume ratio (DVR) for [(18)F]FEDL in peritumoral pancreatic tissue was estimated as 3.57+/-0.60 and 0.94+/-0.72 in sham-operated control pancreas. Comparative analysis of quantitative autoradiographic images and densitometry of immunohistochemically stained and co-registered adjacent tissue sections demonstrated a strong linear correlation between the magnitude of [(18)F]FEDL binding and HIP/PAP expression in corresponding regions (r = 0.88). The in situ analysis demonstrated that at least a 2-4 fold apparent lesion size amplification was achieved for submillimeter tumors and to nearly half a murine pancreas for tumors larger than 3 mm.
  
  
  CONCLUSIONS
  We have demonstrated the feasibility of detection of early pancreatic tumors by non-invasive imaging with [(18)F]FEDL PET/CT of tumor biomarker HIP/PAP over-expressed in peritumoral pancreatic tissue. Non-invasive non-invasive detection of early pancreatic carcinomas with [(18)F]FEDL PET/CT imaging should aid the guidance of biopsies and additional imaging procedures, facilitate the resectability and improve the overall prognosis.
authors: Department of Experimental Diagnostic Imaging, Center for Advanced Biomedical Imaging Research, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors: Leo Garcia
authors: LG
authors: Flores
authors: Susanna
authors: S
authors: Bertolini
authors: Hsin Hsin
authors: HH
authors: Yeh
authors: Daniel
authors: D
authors: Young
authors: Uday
authors: U
authors: Mukhopadhyay
authors: Ashutosh
authors: A
authors: Pal
authors: Yunming
authors: Y
authors: Ying
authors: Andrei
authors: A
authors: Volgin
authors: Aleksandr
authors: A
authors: Shavrin
authors: Suren
authors: S
authors: Soghomonyan
authors: William
authors: W
authors: Tong
authors: William
authors: W
authors: Bornmann
authors: Mian M
authors: MM
authors: Alauddin
authors: Craig
authors: C
authors: Logsdon
authors: Juri G
authors: JG
authors: Gelovani
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism*; D018267:Carcinoma, Acinar Cell / Q000378:metabolism; D005462:Fluorine Radioisotopes / Q000494:pharmacology*; D007785:Lactose / Q000494:pharmacology* / Q000031:analogs & derivatives; D037181:Lectins, C-Type / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D008954:Models, Biological; D009368:Neoplasm Transplantation; D010179:Pancreas / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000175:diagnosis*; D000073718:Pancreatitis-Associated Proteins; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000494:pharmacology*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D014057:Tomography, X-Ray Computed / Q000379:methods*
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D005462:Fluorine Radioisotopes; D037181:Lectins, C-Type; D008024:Ligands; C548885:O-galactopyranosyl-(1-4')-2'-deoxy-2'-fluoroethylglucopyranose; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; D019275:Radiopharmaceuticals; D007785:Lactose