title: Vascular imaging of solid tumors in rats with a radioactive arsenic-labeled antibody that binds exposed phosphatidylserine.
abstract: OBJECTIVE
  We recently reported that anionic phospholipids, principally phosphatidylserine, become exposed on the external surface of vascular endothelial cells in tumors, probably in response to oxidative stresses present in the tumor microenvironment. In the present study, we tested the hypothesis that a chimeric monoclonal antibody that binds phosphatidylserine could be labeled with radioactive arsenic isotopes and used for molecular imaging of solid tumors in rats.
  
  
  METHODS
  Bavituximab was labeled with (74)As (beta(+), T(1/2) 17.8 days) or (77)As (beta(-), T(1/2) 1.6 days) using a novel procedure. The radionuclides of arsenic were selected because their long half-lives are consistent with the long biological half lives of antibodies in vivo and because their chemistry permits stable attachment to antibodies. The radiolabeled antibodies were tested for the ability to image subcutaneous Dunning prostate R3227-AT1 tumors in rats.
  
  
  RESULTS
  Clear images of the tumors were obtained using planar gamma-scintigraphy and positron emission tomography. Biodistribution studies confirmed the specific localization of bavituximab to the tumors. The tumor-to-liver ratio 72 h after injection was 22 for bavituximab compared with 1.5 for an isotype-matched control chimeric antibody of irrelevant specificity. Immunohistochemical studies showed that the bavituximab was labeling the tumor vascular endothelium.
  
  
  CONCLUSIONS
  These results show that radioarsenic-labeled bavituximab has potential as a new tool for imaging the vasculature of solid tumors.
authors.affiliation: Institute of Nuclear Chemistry, Johannes Gutenberg-University of Mainz, Mainz, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Jennewein
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Lewis
authors.forename: Dawen
authors.initials: D
authors.lastname: Zhao
authors.forename: Edward
authors.initials: E
authors.lastname: Tsyganov
authors.forename: Nikolai
authors.initials: N
authors.lastname: Slavine
authors.forename: Jin
authors.initials: J
authors.lastname: He
authors.forename: Linda
authors.initials: L
authors.lastname: Watkins
authors.forename: Vikram D
authors.initials: VD
authors.lastname: Kodibagkar
authors.forename: Sean
authors.initials: S
authors.lastname: O'Kelly
authors.forename: Padmakar
authors.initials: P
authors.lastname: Kulkarni
authors.forename: Peter P
authors.initials: PP
authors.lastname: Antich
authors.forename: Alex
authors.initials: A
authors.lastname: Hermanne
authors.forename: Frank
authors.initials: F
authors.lastname: Rösch
authors.forename: Ralph P
authors.initials: RP
authors.lastname: Mason
authors.forename: Philip E
authors.initials: PE
authors.lastname: Thorpe
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001151:Arsenic / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D008297:Male; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging*; D010718:Phosphatidylserines / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011471:Prostatic Neoplasms / Q000098:blood supply*; D016719:Radioimmunodetection; D011868:Radioisotopes / Q000378:metabolism*; D051381:Rats; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D010718:Phosphatidylserines; D011868:Radioisotopes; D001151:Arsenic