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Title: Imaging Axl expression in pancreatic and prostate cancer xenografts

Abstract

Highlights: •Axl is overexpressed in a variety of cancers. •Axl overexpression confers invasive phenotype. •Axl imaging would be useful for therapeutic guidance and monitoring. •Axl expression imaging is demonstrated in pancreatic and prostate cancer xenografts. •Graded levels of Axl expression imaging is feasible. -- Abstract: The receptor tyrosine kinase Axl is overexpressed in and leads to patient morbidity and mortality in a variety of cancers. Axl–Gas6 interactions are critical for tumor growth, angiogenesis and metastasis. The goal of this study was to investigate the feasibility of imaging graded levels of Axl expression in tumors using a radiolabeled antibody. We radiolabeled anti-human Axl (Axl mAb) and control IgG1 antibodies with {sup 125}I with high specific radioactivity and radiochemical purity, resulting in an immunoreactive fraction suitable for in vivo studies. Radiolabeled antibodies were investigated in severe combined immunodeficient mice harboring subcutaneous CFPAC (Axl{sup high}) and Panc1 (Axl{sup low}) pancreatic cancer xenografts by ex vivo biodistribution and imaging. Based on these results, the specificity of [{sup 125}I]Axl mAb was also validated in mice harboring orthotopic Panc1 or CFPAC tumors and in mice harboring subcutaneous 22Rv1 (Axl{sup low}) or DU145 (Axl{sup high}) prostate tumors by ex vivo biodistribution and imaging studies at 72 hmore » post-injection of the antibody. Both imaging and biodistribution studies demonstrated specific and persistent accumulation of [{sup 125}I]Axl mAb in Axl{sup high} (CFPAC and DU145) expression tumors compared to the Axl{sup low} (Panc1 and 22Rv1) expression tumors. Axl expression in these tumors was further confirmed by immunohistochemical studies. No difference in the uptake of radioactivity was observed between the control [{sup 125}I]IgG1 antibody in the Axl{sup high} and Axl{sup low} expression tumors. These data demonstrate the feasibility of imaging Axl expression in pancreatic and prostate tumor xenografts.« less

Authors:
 [1]; ;  [1];  [2];  [3]
  1. Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD 21287 (United States)
  2. Department of Pathology, Johns Hopkins University, Baltimore, MD 21287 (United States)
  3. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287 (United States)
Publication Date:
OSTI Identifier:
22242267
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 443; Journal Issue: 2; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANTIBODIES; DISEASE INCIDENCE; HARBORS; IODINE 125; MICE; NEOPLASMS; PANCREAS; PROSTATE; RADIOACTIVITY; RADIOCHEMISTRY; RECEPTORS; TYROSINE

Citation Formats

Nimmagadda, Sridhar, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, Pullambhatla, Mrudula, Lisok, Ala, Hu, Chaoxin, Maitra, Anirban, Department of Pathology, Johns Hopkins University, Baltimore, MD 21287, Pomper, Martin G, E-mail: mpomper@jhmi.edu, and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287. Imaging Axl expression in pancreatic and prostate cancer xenografts. United States: N. p., 2014. Web. doi:10.1016/J.BBRC.2013.12.014.
Nimmagadda, Sridhar, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, Pullambhatla, Mrudula, Lisok, Ala, Hu, Chaoxin, Maitra, Anirban, Department of Pathology, Johns Hopkins University, Baltimore, MD 21287, Pomper, Martin G, E-mail: mpomper@jhmi.edu, & Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287. Imaging Axl expression in pancreatic and prostate cancer xenografts. United States. https://doi.org/10.1016/J.BBRC.2013.12.014
Nimmagadda, Sridhar, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, Pullambhatla, Mrudula, Lisok, Ala, Hu, Chaoxin, Maitra, Anirban, Department of Pathology, Johns Hopkins University, Baltimore, MD 21287, Pomper, Martin G, E-mail: mpomper@jhmi.edu, and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287. 2014. "Imaging Axl expression in pancreatic and prostate cancer xenografts". United States. https://doi.org/10.1016/J.BBRC.2013.12.014.
@article{osti_22242267,
title = {Imaging Axl expression in pancreatic and prostate cancer xenografts},
author = {Nimmagadda, Sridhar and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287 and Pullambhatla, Mrudula and Lisok, Ala and Hu, Chaoxin and Maitra, Anirban and Department of Pathology, Johns Hopkins University, Baltimore, MD 21287 and Pomper, Martin G, E-mail: mpomper@jhmi.edu and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287},
abstractNote = {Highlights: •Axl is overexpressed in a variety of cancers. •Axl overexpression confers invasive phenotype. •Axl imaging would be useful for therapeutic guidance and monitoring. •Axl expression imaging is demonstrated in pancreatic and prostate cancer xenografts. •Graded levels of Axl expression imaging is feasible. -- Abstract: The receptor tyrosine kinase Axl is overexpressed in and leads to patient morbidity and mortality in a variety of cancers. Axl–Gas6 interactions are critical for tumor growth, angiogenesis and metastasis. The goal of this study was to investigate the feasibility of imaging graded levels of Axl expression in tumors using a radiolabeled antibody. We radiolabeled anti-human Axl (Axl mAb) and control IgG1 antibodies with {sup 125}I with high specific radioactivity and radiochemical purity, resulting in an immunoreactive fraction suitable for in vivo studies. Radiolabeled antibodies were investigated in severe combined immunodeficient mice harboring subcutaneous CFPAC (Axl{sup high}) and Panc1 (Axl{sup low}) pancreatic cancer xenografts by ex vivo biodistribution and imaging. Based on these results, the specificity of [{sup 125}I]Axl mAb was also validated in mice harboring orthotopic Panc1 or CFPAC tumors and in mice harboring subcutaneous 22Rv1 (Axl{sup low}) or DU145 (Axl{sup high}) prostate tumors by ex vivo biodistribution and imaging studies at 72 h post-injection of the antibody. Both imaging and biodistribution studies demonstrated specific and persistent accumulation of [{sup 125}I]Axl mAb in Axl{sup high} (CFPAC and DU145) expression tumors compared to the Axl{sup low} (Panc1 and 22Rv1) expression tumors. Axl expression in these tumors was further confirmed by immunohistochemical studies. No difference in the uptake of radioactivity was observed between the control [{sup 125}I]IgG1 antibody in the Axl{sup high} and Axl{sup low} expression tumors. These data demonstrate the feasibility of imaging Axl expression in pancreatic and prostate tumor xenografts.},
doi = {10.1016/J.BBRC.2013.12.014},
url = {https://www.osti.gov/biblio/22242267}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 2,
volume = 443,
place = {United States},
year = {Fri Jan 10 00:00:00 EST 2014},
month = {Fri Jan 10 00:00:00 EST 2014}
}