Thititip Tippayamontri1, Rami Kotb2, Léon Sanche1, Benoit Paquette3. 1. 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. 2. Department of Systemic Therapy, BC Cancer Agency's Vancouver Island Centre, Victoria, BC, Canada. 3. 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.
Abstract
AIM: 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. MATERIALS AND 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. CONCLUSION: 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. Copyright
AIM: 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. MATERIALS AND METHODS:Nude mice implanted with humancolorectal 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. CONCLUSION: 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. Copyright