title: Imaging Axl expression in pancreatic and prostate cancer xenografts.
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 (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(high)) and Panc1 (Axl(low)) pancreatic cancer xenografts by ex vivo biodistribution and imaging. Based on these results, the specificity of [(125)I]Axl mAb was also validated in mice harboring orthotopic Panc1 or CFPAC tumors and in mice harboring subcutaneous 22Rv1 (Axl(low)) or DU145 (Axl(high)) prostate tumors by ex vivo biodistribution and imaging studies at 72h post-injection of the antibody. Both imaging and biodistribution studies demonstrated specific and persistent accumulation of [(125)I]Axl mAb in Axl(high) (CFPAC and DU145) expression tumors compared to the Axl(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 [(125)I]IgG1 antibody in the Axl(high) and Axl(low) expression tumors. These data demonstrate the feasibility of imaging Axl expression in pancreatic and prostate tumor xenografts.
authors: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD 21287, United States; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, United States. Electronic address: snimmag1@jhmi.edu.
authors: Sridhar
authors: S
authors: Nimmagadda
authors: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD 21287, United States.
authors: Mrudula
authors: M
authors: Pullambhatla
authors: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD 21287, United States.
authors: Ala
authors: A
authors: Lisok
authors: Department of Pathology, Johns Hopkins University, Baltimore, MD 21287, United States.
authors: Chaoxin
authors: C
authors: Hu
authors: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, United States; Department of Pathology, Johns Hopkins University, Baltimore, MD 21287, United States.
authors: Anirban
authors: A
authors: Maitra
authors: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD 21287, United States; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, United States. Electronic address: mpomper@jhmi.edu.
authors: Martin G
authors: MG
authors: Pomper
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D008297:Male; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D057054:Molecular Imaging / Q000379:methods*; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D011877:Radionuclide Imaging; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D014018:Tissue Distribution; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D000094963:Axl Receptor Tyrosine Kinase; C000722290:AXL receptor tyrosine kinase, mouse
keywords: Axl; Gas6; ImmunoPET; Molecular imaging; Receptor tyrosine kinase