title: Target-specific agents imaging ectopic and orthotopic human pancreatic cancer xenografts.
abstract: OBJECTIVE
  This study aimed to develop target-specific binding agents for in vitro and in vivo imaging of human pancreatic cancer.
  
  
  METHODS
  A monoclonal neutrophil gelatinase-associated lipocalin (NGAL)-specific antibody and a peptide specific for matrix metalloproteinase (MMP) were labeled with a near-infrared dye for in vitro and in vivo imaging studies. Fluorescence or confocal microscopy was used to determine antibody or peptide binding and internalization of agents into human AsPC-1, Panc-1, and MiaPaCa pancreatic cancer cell lines and in mice bearing ectopic or orthotopic pancreatic tumor transplants.
  
  
  RESULTS
  Both the NGAL-specific antibody and MMP peptide bound to pancreatic cancer cells with high specificity; most NGAL-specific antibody localized to the cytosol. In vivo imaging results demonstrated high signal intensity of both agents bound to the tumor. The average tumortr-to-background ratio of antibody and peptide was 1.29 and 2.86, respectively. Signal was also detectable in the liver, kidneys, and bladder.
  
  
  CONCLUSIONS
  Both NGAL-specific antibody and MMP peptide bound to cancer cells, and the labeled antibody was internalized. These results demonstrate that both agents can be used to enhance detection of human pancreatic cancer xenografts. However, the biodistribution patterns of these agents might limit their use in research and clinical practice.
authors.affiliation: Department of Radiology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Lin
authors.forename: Sushovan
authors.initials: S
authors.lastname: Guha
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Tong
authors.forename: Arlin G
authors.initials: AG
authors.lastname: Cameron
authors.forename: Fujun
authors.initials: F
authors.lastname: Zhang
authors.forename: Xiuchun
authors.initials: X
authors.lastname: Qiu
authors.forename: Chaoxia
authors.initials: C
authors.lastname: Zou
authors.forename: Xu
authors.initials: X
authors.lastname: Gao
authors.forename: Michel E
authors.initials: ME
authors.lastname: Mawad
authors.forename: Shi
authors.initials: S
authors.lastname: Ke
mesh_terms: D000209:Acute-Phase Proteins / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000276:immunology; D020782:Matrix Metalloproteinases / Q000276:immunology; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000276:immunology; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
chemical_list: D000209:Acute-Phase Proteins; D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D020782:Matrix Metalloproteinases