Imaging Axl expression in pancreatic and prostate cancer xenografts |
| |
Authors: | Sridhar Nimmagadda Mrudula Pullambhatla Ala Lisok Chaoxin Hu Anirban Maitra Martin G Pomper |
| |
Institution: | 1. Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD 21287, United States;2. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, United States;3. Department of Pathology, Johns Hopkins University, Baltimore, MD 21287, United States |
| |
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 125I 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 (Axlhigh) and Panc1 (Axllow) pancreatic cancer xenografts by ex vivo biodistribution and imaging. Based on these results, the specificity of 125I]Axl mAb was also validated in mice harboring orthotopic Panc1 or CFPAC tumors and in mice harboring subcutaneous 22Rv1 (Axllow) or DU145 (Axlhigh) 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 125I]Axl mAb in Axlhigh (CFPAC and DU145) expression tumors compared to the Axllow (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 125I]IgG1 antibody in the Axlhigh and Axllow expression tumors. These data demonstrate the feasibility of imaging Axl expression in pancreatic and prostate tumor xenografts. |
| |
Keywords: | Molecular imaging ImmunoPET Receptor tyrosine kinase Axl Gas6 |
本文献已被 ScienceDirect 等数据库收录! |
|