Pharmacokinetic modeling for optimization of radioimmunotherapy – macroscopic and microscopic approach
(2005)Medical Physics Programme
- Abstract (Swedish)
- Purpose: For evaluation, development and optimization of treatment strategies in radionuclide therapy, it is useful to study and model the pharmacokinetics of the therapeutic agent. The aim of this study was to create models for describing the pharmacokinetics of monoclonal antibodies used for radioimmunotherapy.Method: Two models, based on very different modeling approaches, are presented in this thesis. The first model is a macroscopic compartmental model, i.e. it addresses the pharmacokinetic behavior in a macroscopic scale. The model is not based on actual physiological processes, but is rather a simplified method to describe the pharmacokinetics that can be “seen” with imaging techniques. The basis for the model is measurements of... (More)
- Purpose: For evaluation, development and optimization of treatment strategies in radionuclide therapy, it is useful to study and model the pharmacokinetics of the therapeutic agent. The aim of this study was to create models for describing the pharmacokinetics of monoclonal antibodies used for radioimmunotherapy.Method: Two models, based on very different modeling approaches, are presented in this thesis. The first model is a macroscopic compartmental model, i.e. it addresses the pharmacokinetic behavior in a macroscopic scale. The model is not based on actual physiological processes, but is rather a simplified method to describe the pharmacokinetics that can be “seen” with imaging techniques. The basis for the model is measurements of activity distributions in a clinical study of radioimmunotherapy of B-cell lymphoma, and the parameters of the model is iteratively calculated by the model fitting to these data. In the clinical study, extracorporeal adsorbtion (ECAT) is used to lower the radiation dose to the normal organs and improve the therapeutic ratio. This is also implemented in the model as a perturbation, and evaluated.The second model is a microscopic pharmacokinetic model for studying the pharmacokinetics in a small prevascular tumor nodule, for example a micrometastases. The model is theoretical and based on physiological parameters and the basic mechanisms of transport. The effect of ECAT is evaluated in the microscopic scale and an investigation is made on how the different parameters of the model influence the accumulation of antibodies in the nodule.Results: The macroscopic compartmental model is successfully fit to the clinical data. In the case of therapy, the model could accurately describe the measured data during the ECAT procedure. By fitting the model to diagnostic data and add the ECAT procedure as a perturbation to the model, the therapeutic data could be predicted. In the microscopic model, it is found that the time for saturation of a microscopic cluster of tumor cells could be described as a simple function of the model parameters.Conclusion: The overall good fit to the therapy data indicates that the macroscopic model in fact, despite its simplicity, is suitable for describing the pharmacokinetics of monoclonal antibodies in radioimmunotherapy. As the measured therapy data could be predicted by the use of diagnostic data by adding ECAT as a perturbation to the model, it might become useful as a tool for evaluation and optimization of clinical strategies. The microscopic pharmacokinetic model can be used, by combining it with dosimetry, to optimize and evaluate different treatment strategies in the microscopic scale (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/2156950
- author
- Nickel, Mattias
- supervisor
- organization
- year
- 2005
- type
- H2 - Master's Degree (Two Years)
- subject
- keywords
- Nukleärmedicin
- language
- English
- id
- 2156950
- date added to LUP
- 2011-09-13 15:21:26
- date last changed
- 2011-09-13 15:21:26
@misc{2156950,
abstract = {{Purpose: For evaluation, development and optimization of treatment strategies in radionuclide therapy, it is useful to study and model the pharmacokinetics of the therapeutic agent. The aim of this study was to create models for describing the pharmacokinetics of monoclonal antibodies used for radioimmunotherapy.Method: Two models, based on very different modeling approaches, are presented in this thesis. The first model is a macroscopic compartmental model, i.e. it addresses the pharmacokinetic behavior in a macroscopic scale. The model is not based on actual physiological processes, but is rather a simplified method to describe the pharmacokinetics that can be “seen” with imaging techniques. The basis for the model is measurements of activity distributions in a clinical study of radioimmunotherapy of B-cell lymphoma, and the parameters of the model is iteratively calculated by the model fitting to these data. In the clinical study, extracorporeal adsorbtion (ECAT) is used to lower the radiation dose to the normal organs and improve the therapeutic ratio. This is also implemented in the model as a perturbation, and evaluated.The second model is a microscopic pharmacokinetic model for studying the pharmacokinetics in a small prevascular tumor nodule, for example a micrometastases. The model is theoretical and based on physiological parameters and the basic mechanisms of transport. The effect of ECAT is evaluated in the microscopic scale and an investigation is made on how the different parameters of the model influence the accumulation of antibodies in the nodule.Results: The macroscopic compartmental model is successfully fit to the clinical data. In the case of therapy, the model could accurately describe the measured data during the ECAT procedure. By fitting the model to diagnostic data and add the ECAT procedure as a perturbation to the model, the therapeutic data could be predicted. In the microscopic model, it is found that the time for saturation of a microscopic cluster of tumor cells could be described as a simple function of the model parameters.Conclusion: The overall good fit to the therapy data indicates that the macroscopic model in fact, despite its simplicity, is suitable for describing the pharmacokinetics of monoclonal antibodies in radioimmunotherapy. As the measured therapy data could be predicted by the use of diagnostic data by adding ECAT as a perturbation to the model, it might become useful as a tool for evaluation and optimization of clinical strategies. The microscopic pharmacokinetic model can be used, by combining it with dosimetry, to optimize and evaluate different treatment strategies in the microscopic scale}},
author = {{Nickel, Mattias}},
language = {{eng}},
note = {{Student Paper}},
title = {{Pharmacokinetic modeling for optimization of radioimmunotherapy – macroscopic and microscopic approach}},
year = {{2005}},
}