Imaging metastatic cancer models with PET/SPECT/CT and optical imaging
I. The purpose of the experiment/project:
The purpose of this experiment is to validate PET/SPECT/CT imaging protocols, target-specific tracers for imaging of the metastatic model and confirm the model characterization made in FOTS ID14509 using IHC techniques.
II. The expected adverse effects on the animals:
All models used in this study well be evaluated in FOTS ID14509. Only models with no significant impact on animal health will be used. We still will use a score scheme for assessment of animal well-being to mitigate the adverse effects, such as general health decline and specific symptoms associated with site-specific metastasis.
III. The expected scientific benefits or benefits for society:
In this study we will evaluate imaging techniques, a tracer and compare the results with model evaluation done in FOTS ID14509 using IHC method. Use of imaging for tumor growth evaluation, evaluation of treatment response and biodistribution of the radiolabelled drug products will allow us to reduce the number of animals required for longitudinal biodistribution evaluation as well as refine the techniques reducing the number of intervention required for treatment assessment. We will also might get incite into processes that can't be evaluated during postmortem tissue analysis.
IV. The number of animals and species:
In this study we aim to evaluate using imaging up to 10 models, evaluated in FOTS ID14509. For each model we will perform tracer and model evaluation with 3 mice, determining tracer uptake and optimal time points for imaging, followed by the expansion cohort adding 9 mice to evaluation to collect enough data to perform quantitative analysis and comparison with postmortem tissue analysis using immunohistochemistry. For each model we would then need 3 + 9 = 12 mice. We assume take rate to be around 70%, we would need 17 mice per model. The take rate calculations will be adjusted based on the results from FOTS ID14509. In total we apply for 17 mice x 10 models = 170 mice.
V. How will the requirements for 3R be accomplished by the experiment/project:
All the models considered for evaluation will undergo evaluation consisting of literature review to identify whether the cell line is suitable for the metastatic model, in vitro analysis such as target binding assays, in vitro efficacy etc. and project value evaluation. No models will be established unless necessary for biodistriburtion/efficacy studies.
Each experiment is divided into two part - evaluation of the tracer in a model with 3 mice followed by an expansion with evaluation in 9 mice at 3 different time point. A second part of the evaluation will not be conducted if no tracer uptake in the metastatic model will be found. As a result of the study we will generate a toolbox for future biodistribution and efficacy studies that will allow us to reduce the number of animals required for these studies.
The techniques used in this study are refined, and study participant has received specialized training for the procedures in this study, in addition to long experience with comparable studies.
We would like to change the PI responsibility of this FOTS to Ana Oteiza
The purpose of this experiment is to validate PET/SPECT/CT imaging protocols, target-specific tracers for imaging of the metastatic model and confirm the model characterization made in FOTS ID14509 using IHC techniques.
II. The expected adverse effects on the animals:
All models used in this study well be evaluated in FOTS ID14509. Only models with no significant impact on animal health will be used. We still will use a score scheme for assessment of animal well-being to mitigate the adverse effects, such as general health decline and specific symptoms associated with site-specific metastasis.
III. The expected scientific benefits or benefits for society:
In this study we will evaluate imaging techniques, a tracer and compare the results with model evaluation done in FOTS ID14509 using IHC method. Use of imaging for tumor growth evaluation, evaluation of treatment response and biodistribution of the radiolabelled drug products will allow us to reduce the number of animals required for longitudinal biodistribution evaluation as well as refine the techniques reducing the number of intervention required for treatment assessment. We will also might get incite into processes that can't be evaluated during postmortem tissue analysis.
IV. The number of animals and species:
In this study we aim to evaluate using imaging up to 10 models, evaluated in FOTS ID14509. For each model we will perform tracer and model evaluation with 3 mice, determining tracer uptake and optimal time points for imaging, followed by the expansion cohort adding 9 mice to evaluation to collect enough data to perform quantitative analysis and comparison with postmortem tissue analysis using immunohistochemistry. For each model we would then need 3 + 9 = 12 mice. We assume take rate to be around 70%, we would need 17 mice per model. The take rate calculations will be adjusted based on the results from FOTS ID14509. In total we apply for 17 mice x 10 models = 170 mice.
V. How will the requirements for 3R be accomplished by the experiment/project:
All the models considered for evaluation will undergo evaluation consisting of literature review to identify whether the cell line is suitable for the metastatic model, in vitro analysis such as target binding assays, in vitro efficacy etc. and project value evaluation. No models will be established unless necessary for biodistriburtion/efficacy studies.
Each experiment is divided into two part - evaluation of the tracer in a model with 3 mice followed by an expansion with evaluation in 9 mice at 3 different time point. A second part of the evaluation will not be conducted if no tracer uptake in the metastatic model will be found. As a result of the study we will generate a toolbox for future biodistribution and efficacy studies that will allow us to reduce the number of animals required for these studies.
The techniques used in this study are refined, and study participant has received specialized training for the procedures in this study, in addition to long experience with comparable studies.
We would like to change the PI responsibility of this FOTS to Ana Oteiza