Target-specific agents imaging ectopic and orthotopic human pancreatic cancer xenografts.

Abstract:

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.

journal_name

Pancreas

journal_title

Pancreas

authors

Wang W,Lin J,Guha S,Tong Z,Cameron AG,Zhang F,Qiu X,Zou C,Gao X,Mawad ME,Ke S

doi

10.1097/MPA.0b013e31821f6b14

subject

Has Abstract

pub_date

2011-07-01 00:00:00

pages

689-94

issue

5

eissn

0885-3177

issn

1536-4828

journal_volume

40

pub_type

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