Comparison of different radioactive isotopes for targeting treatment of cancer
I. The purpose of the experiment/project:
The aim of this study is to compare the pharmacokinetic profile, biodistributuion and efficacy of targeting conjugates labeled with different radioactive isotopes commonly used and that can potentially be used for radioimmunotherapy (RIT). Typically, alpha- and beta-particle emitting isotopes are used for systemic RIT have a particle range around 0.04-3mm allowing specific targeting of tumor cells. Differences in range between alpha and beta particles, biological half-life time for targeting conjugates and radioisotopes contributed to differences in doses to different parts of the tumor and other organs, leading to differences in efficacy and toxicity profiles. In this study, we will generate data for head-to-head comparison of these parameters for several different targeting conjugates and different isotopes.
II. The expected adverse effects on the animals:
Three main adverse effects for the mice in this experiment are ulcerations of the tumors, weight reduction and reduction in white blood cell count. To eliminate the adverse effects, we will daily follow the mice well-being, sacrificing the animals with the first signs of ulcer, distress or 15% weight reduction. All doses used in this study are below the doses causing dose-limiting toxicity.
III. The expected scientific benefits or benefits for society:
Selection of radio-emitting isotope, pairing it with the targeting moiety, calculating radioactive dose to tumor and risk organs is a challenging exercise. This is due to many factors that has to be taken into consideration. Data generated in the current study will allow us to select isotopes for further development. Moreover, no data comparing these widely used isotopes exists in the literature and will be useful for many research groups working in the field. A paper describing the experiment and the results will be published in a journal allowing a wide public to access this knowledge.
IV. The number of animals and species:
In this study we aim to utilize a three different cancer models with different properties with regards to target expression, perfusion, growth rate etc. Both the PK/biodistribution and efficacy studies of will be performed. We will use 645 athymic nude mice in this study.
V. How will the requirements for 3R be accomplished by the experiment/project:
Multiple in vitro studies will be conducted to prove the efficacy, characterization and specific killing in all 3 cell lines before the conduction of the in vivo experiments. We have already utilized all 3 models in vivo, and have good knowledge of this models about group size, timing of treatment etc. The number of mice in both efficacy and biodistribution parts of the study are reduced to minimum. The technicians conducting the study have long experience with similar studies using well-refined techniques.
The aim of this study is to compare the pharmacokinetic profile, biodistributuion and efficacy of targeting conjugates labeled with different radioactive isotopes commonly used and that can potentially be used for radioimmunotherapy (RIT). Typically, alpha- and beta-particle emitting isotopes are used for systemic RIT have a particle range around 0.04-3mm allowing specific targeting of tumor cells. Differences in range between alpha and beta particles, biological half-life time for targeting conjugates and radioisotopes contributed to differences in doses to different parts of the tumor and other organs, leading to differences in efficacy and toxicity profiles. In this study, we will generate data for head-to-head comparison of these parameters for several different targeting conjugates and different isotopes.
II. The expected adverse effects on the animals:
Three main adverse effects for the mice in this experiment are ulcerations of the tumors, weight reduction and reduction in white blood cell count. To eliminate the adverse effects, we will daily follow the mice well-being, sacrificing the animals with the first signs of ulcer, distress or 15% weight reduction. All doses used in this study are below the doses causing dose-limiting toxicity.
III. The expected scientific benefits or benefits for society:
Selection of radio-emitting isotope, pairing it with the targeting moiety, calculating radioactive dose to tumor and risk organs is a challenging exercise. This is due to many factors that has to be taken into consideration. Data generated in the current study will allow us to select isotopes for further development. Moreover, no data comparing these widely used isotopes exists in the literature and will be useful for many research groups working in the field. A paper describing the experiment and the results will be published in a journal allowing a wide public to access this knowledge.
IV. The number of animals and species:
In this study we aim to utilize a three different cancer models with different properties with regards to target expression, perfusion, growth rate etc. Both the PK/biodistribution and efficacy studies of will be performed. We will use 645 athymic nude mice in this study.
V. How will the requirements for 3R be accomplished by the experiment/project:
Multiple in vitro studies will be conducted to prove the efficacy, characterization and specific killing in all 3 cell lines before the conduction of the in vivo experiments. We have already utilized all 3 models in vivo, and have good knowledge of this models about group size, timing of treatment etc. The number of mice in both efficacy and biodistribution parts of the study are reduced to minimum. The technicians conducting the study have long experience with similar studies using well-refined techniques.