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Tytuł:
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Target-specific agents imaging ectopic and orthotopic human pancreatic cancer xenografts.
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Autorzy:
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Wang W; Department of Radiology, Baylor College of Medicine, Houston, TX, USA.
Lin J
Guha S
Tong Z
Cameron AG
Zhang F
Qiu X
Zou C
Gao X
Mawad ME
Ke S
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Źródło:
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Pancreas [Pancreas] 2011 Jul; Vol. 40 (5), pp. 689-94.
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Typ publikacji:
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Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
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Język:
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English
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Imprint Name(s):
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Publication: Hagerstown, MD : Lippincott Williams & Wilkins
Original Publication: [New York, N.Y.] : Raven Press, [c1986-
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MeSH Terms:
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Pancreatic Neoplasms/*diagnosis
Acute-Phase Proteins/immunology ; Animals ; Antibodies, Monoclonal ; Biomarkers, Tumor/immunology ; Biomarkers, Tumor/metabolism ; Cell Line, Tumor ; Female ; Humans ; Lipocalin-2 ; Lipocalins/immunology ; Matrix Metalloproteinases/immunology ; Mice ; Mice, Nude ; Microscopy, Confocal ; Microscopy, Fluorescence ; Pancreatic Neoplasms/metabolism ; Proto-Oncogene Proteins/immunology ; Tissue Distribution ; Transplantation, Heterologous
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Grant Information:
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DK56338 United States DK NIDDK NIH HHS
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Substance Nomenclature:
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0 (Acute-Phase Proteins)
0 (Antibodies, Monoclonal)
0 (Biomarkers, Tumor)
0 (LCN2 protein, human)
0 (Lipocalin-2)
0 (Lipocalins)
0 (Proto-Oncogene Proteins)
EC 3.4.24.- (Matrix Metalloproteinases)
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Entry Date(s):
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Date Created: 20110610 Date Completed: 20111024 Latest Revision: 20161125
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Update Code:
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20240104
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DOI:
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10.1097/MPA.0b013e31821f6b14
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PMID:
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21654540
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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.