title: Treatment with a vascular disrupting agent does not increase recruitment of indium labelled human endothelial outgrowth cells in an experimental tumour model.
abstract: BACKGROUND
  The effect of vascular disrupting agents in tumour therapy depends on both the immediate vascular shutdown, and on the following re-vascularization of the tumour. The aim of this study was to use a tumour model to investigate whether endothelial outgrowth cells (EOCs) influenced the short term treatment efficiency of combretastatin A-4 disodium phosphate (CA4P) and 5,6-dimethylxanthenone-4-acetic acid (DMXAA) by increasing EOC tumour recruitment.
  
  
  METHODS
  In order to visualize the recruitment of EOCs to the tumours, umbilical cord blood derived human EOCs were labelled with 111Indium-tropolone in a dose of 0.37 MBq pr 3×106 cells and were injected intravenously into mice carrying a C3H mammary carcinoma on their right rear foot. DMXAA and CA4P in different concentrations and at different exposure times were used to create a hypoxic environment in the C3H mammary carcinoma in the mice. Three different mice strains with various degrees of functional immune system were used to study the homing capability of EOCs.
  
  
  RESULTS
  Our data showed that approximately 4% of the total injected radioactive dose per gram of tissue was found in the tumour after treatment with CA4P and DMXAA. Regardless of the concentration and the treatment duration, CA4P did not increase EOC recruitment to the tumour in comparison to EOC recruitment in control tumours in any of the 3 mice strains studied.
  
  
  CONCLUSIONS
  Our data showed that regardless of the grade of the immune system, ranging from a fully working to a fully compromised immune system, treatment with CA4P did not increase recruitment of xenotransplanted EOCs to tumour tissue.
authors.affiliation: MR-Research Centre, Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark. Lotte@mr.au.dk.
authors.forename: Lotte B
authors.initials: LB
authors.lastname: Bertelsen
authors.forename: Anja B
authors.initials: AB
authors.lastname: Bohn
authors.forename: Yuan Yuan
authors.initials: YY
authors.lastname: Shen
authors.forename: Lise
authors.initials: L
authors.lastname: Falborg
authors.forename: Hans
authors.initials: H
authors.lastname: Stødkilde-Jørgensen
authors.forename: Michael R
authors.initials: MR
authors.lastname: Horsman
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D002277:Carcinoma / Q000188:drug therapy*; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D058948:Cell Tracking; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology / Q000637:transplantation; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D007205:Indium Radioisotopes; D051379:Mice; D008819:Mice, Nude; D013267:Stilbenes / Q000494:pharmacology*; D044004:Xanthones / Q000494:pharmacology*
chemical_list: D020533:Angiogenesis Inhibitors; D007205:Indium Radioisotopes; D013267:Stilbenes; D044004:Xanthones; C066668:vadimezan; C058728:fosbretabulin