Bio-distribution and efficacy studies of radioimmunotherapy anti-cancer drugs
1 Formål
Breast and colorectal cancer are among the most common forms of cancer as of 2020, and new treatments are necessary to improve the survival of the patients suffering from these types of cancer. Use of radioactive targeted therapy, where radioactivity is linked to antibodies have shown great promise for different cancer types. We want to test novel radioactive substances linked to antibodies targeting proteins frequently expressed in breast and colorectal cancer and investigate their biodistribution and treatment efficacy on different tumor models.
2 Skadevirkninger
We will first do maximal tolerable dose studies to find a dose that is tolerated by the mice which we will use for later treatment and biodistribution experiments. The breast and subcutanous colorectal cancers have previously shown to be well tolerated by mice and will not lead to cachexia. The mice will be sacrificed when they have large tumors. Tumors growing intraperitoneally , inthe lungs or in the liver will cause weight loss in the mice, but they will be checked frequently and sacrificed when necessary.
3 Forventet nytteverdi
Breast and colorectal cancer are among the most common forms of cancer, and new treatment strategies are necessary to improve the survival for these patient groups. By using radioactive therapy targeting common biomarkers expressed in breast or colorectal cancer it is possible that this will later improve the survival of patients. Colorectal cancer will often metastasize to the liver, lung and peritoneal cavity, and the drugs will also be investigated in setting mimicking liver, lung and peritoneal metastases asthis is more similar to the clinical situation.
4 Antall dyr og art
1284athymic nude foxn nu
5 Hvordan etterleve 3R
Reduction: The number of mice is kept to a minimum while still being able to see potential differences after treatment. The number of animals necessary in each group is based on previous experiments with these models.
Replacement: In vitro experiements have been performed, but it is now necessary to use in vivo experiments to investigate how the therapy will function in more complex and more clinical relevant settings.
Refinement: The mice receive cardboard houses and paper to make nests. sevofluran is used instead of zoletil for anasthesia. Mice are given analgesia after surgery. A plan for monitoring the well being of the mice as well as humane endpoints are in place to make sure that any discomfort the animals might experience due to engraftment of tumor tissue/cells is kept to a minimum.
The mice will be monitored daily by experienced personel, and sacrificed when necessary.
Breast and colorectal cancer are among the most common forms of cancer as of 2020, and new treatments are necessary to improve the survival of the patients suffering from these types of cancer. Use of radioactive targeted therapy, where radioactivity is linked to antibodies have shown great promise for different cancer types. We want to test novel radioactive substances linked to antibodies targeting proteins frequently expressed in breast and colorectal cancer and investigate their biodistribution and treatment efficacy on different tumor models.
2 Skadevirkninger
We will first do maximal tolerable dose studies to find a dose that is tolerated by the mice which we will use for later treatment and biodistribution experiments. The breast and subcutanous colorectal cancers have previously shown to be well tolerated by mice and will not lead to cachexia. The mice will be sacrificed when they have large tumors. Tumors growing intraperitoneally , inthe lungs or in the liver will cause weight loss in the mice, but they will be checked frequently and sacrificed when necessary.
3 Forventet nytteverdi
Breast and colorectal cancer are among the most common forms of cancer, and new treatment strategies are necessary to improve the survival for these patient groups. By using radioactive therapy targeting common biomarkers expressed in breast or colorectal cancer it is possible that this will later improve the survival of patients. Colorectal cancer will often metastasize to the liver, lung and peritoneal cavity, and the drugs will also be investigated in setting mimicking liver, lung and peritoneal metastases asthis is more similar to the clinical situation.
4 Antall dyr og art
1284athymic nude foxn nu
5 Hvordan etterleve 3R
Reduction: The number of mice is kept to a minimum while still being able to see potential differences after treatment. The number of animals necessary in each group is based on previous experiments with these models.
Replacement: In vitro experiements have been performed, but it is now necessary to use in vivo experiments to investigate how the therapy will function in more complex and more clinical relevant settings.
Refinement: The mice receive cardboard houses and paper to make nests. sevofluran is used instead of zoletil for anasthesia. Mice are given analgesia after surgery. A plan for monitoring the well being of the mice as well as humane endpoints are in place to make sure that any discomfort the animals might experience due to engraftment of tumor tissue/cells is kept to a minimum.
The mice will be monitored daily by experienced personel, and sacrificed when necessary.