OBJECTIVES: 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.
OBJECTIVES: This study aimed to develop target-specific binding agents for in vitro and in vivo imaging of humanpancreatic 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 humanpancreatic cancer xenografts. However, the biodistribution patterns of these agents might limit their use in research and clinical practice.
Authors: Sukhwinder Kaur; Neil Sharma; Shiv Ram Krishn; Imay Lakshmanan; Satyanarayana Rachagani; Michael J Baine; Lynette M Smith; Subodh M Lele; Aaron R Sasson; Sushovan Guha; Kavita Mallya; Judy M Anderson; Michael A Hollingsworth; Surinder K Batra Journal: Clin Cancer Res Date: 2013-11-15 Impact factor: 12.531
Authors: Henricus J M Handgraaf; Martin C Boonstra; Arian R Van Erkel; Bert A Bonsing; Hein Putter; Cornelis J H Van De Velde; Alexander L Vahrmeijer; J Sven D Mieog Journal: Biomed Res Int Date: 2014-07-15 Impact factor: 3.411