title: New therapeutic possibilities of combined treatment of radiotherapy with oxaliplatin and its liposomal formulation, Lipoxal™, in rectal cancer using xenograft in nude mice.
abstract: OBJECTIVE
  To determine the benefits of irradiation at the time of maximum linking of oxaliplatin to the DNA of tumor cells, and evaluate the potential of its liposomal formulation, Lipoxal™, for chemoradiation therapy.
  
  
  METHODS
  Nude mice implanted with human colorectal carcinoma HCT116 cells were injected with oxaliplatin or Lipoxal™. The amount of platinum in tumor, tumoral DNA, normal tissues and blood was measured 4, 24, 48, 72 and 96 h later by inductively coupled plasma mass spectrometry. The effect of concomitant radiotherapy was assessed as tumor growth delay resulting from irradiation 4, 24 and 48 h after drug administration.
  
  
  RESULTS
  While the amount of platinum in the tumor reached a peak at 4 h after injection and declined over time, the concentration of oxaliplatin-DNA adducts reached two maxima observed at 4 h and 48 h after drug administration, a behavior not observed with Lipoxal™. The greatest combined effect was obtained when radiation was given at 48 h after drug injection, resulting in an increase of tumor growth delay by factors of 3.71 and 3.33 for treatments with oxaliplatin and Lipoxal™, respectively.
  
  
  CONCLUSIONS
  Our results confirm the importance of irradiating a tumor when the concentration of oxaliplatin bound to tumor DNA is maximal. This finding should have a significant impact on the design of more efficient chemoradiation treatment protocols and should be further explored in clinical studies.
authors.affiliation: Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Sherbrooke University, Sherbrooke, QC, Canada Center for Research in Radiotherapy, Faculty of Medicine and Health Sciences, Sherbrooke University, Sherbrooke, QC, Canada.
authors.forename: Thititip
authors.initials: T
authors.lastname: Tippayamontri
authors.affiliation: Department of Systemic Therapy, BC Cancer Agency's Vancouver Island Centre, Victoria, BC, Canada.
authors.forename: Rami
authors.initials: R
authors.lastname: Kotb
authors.affiliation: Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Sherbrooke University, Sherbrooke, QC, Canada Center for Research in Radiotherapy, Faculty of Medicine and Health Sciences, Sherbrooke University, Sherbrooke, QC, Canada.
authors.forename: Léon
authors.initials: L
authors.lastname: Sanche
authors.affiliation: Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Sherbrooke University, Sherbrooke, QC, Canada Center for Research in Radiotherapy, Faculty of Medicine and Health Sciences, Sherbrooke University, Sherbrooke, QC, Canada Benoit.Paquette@USherbrooke.ca.
authors.forename: Benoit
authors.initials: B
authors.lastname: Paquette
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D059248:Chemoradiotherapy; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D006801:Humans; D008081:Liposomes; D008297:Male; D051379:Mice; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000077150:Oxaliplatin; D012004:Rectal Neoplasms / Q000473:pathology / Q000628:therapy*; D047368:Tumor Burden / Q000187:drug effects / Q000528:radiation effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D008081:Liposomes; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin
keywords: Concomitant chemoradiation therapy; Lipoxal™; colorectal cancer; oxaliplatin