Use of physiologically based radiopharmacokinetic (PBRPK) models to simulate radiopharmaceutical therapies
department or school: Applied Science, Faculty of
department or school: Biomedical Engineering, School of
data provider: DSpace
degree campus: UBCV
creator: Fele-Paranj, Ali
issued: 2024-01-15T17:32:16Z
issued: 2023
related degree: Master of Applied Science - MASc
degree grantor: University of British Columbia
description: In this thesis, we developed a computational framework using physiologically based pharmacokinetic (PBPK) models to study radiopharmaceutical kinetics in the body. To handle the complexity of PBPK models (over 100 differential equations), a scalable modeling notation called the "reaction graph" is introduced. Implemented in Matlab's Simbiology module and shared in the systems biology markup language (SBML) format, this notation enables easy model reproduction. Referred to as the physiologically based radiopharmacokinetic model (PBRPK), it is fine-tuned specifically for radiopharmaceuticals. Using the PBRPK model and literature-based parameters, we addressed three key questions in radiopharmaceutical therapy. First, we systematically studied the interaction between hot and cold species and its impact on absorbed dose in tumors and organs at risk (OARs) and we found out that tumor receptor density and volume influence the degree of competition and the average absorbed dose in tumors and OARs in a way that lower receptor density (or lower tumor volume) leads to more dominant competition between hot and cold species that is the absorbed dose by tumor highly depends on the number of cold ligands injected to the patient. Next, the effect of injecting radiopharmaceuticals in smaller portions and with specific timing is investigated. We found that bolus injection leads to non-efficient receptor binding and sub-optimal delivered doses to the tumor and organs at risk. However, we found that injecting in several smaller portions leads to a higher absorbed dose by tumors and organs at risk. So multi-bolus injection can be thought of as a tool that increases the delivered dose to the tumor and OAR without any differential effect (delivering mode dose to the tumor and sparing OAR) Finally, the PBRPK model is used to simulate the impact of albumin affinity on radiopharmaceutical kinetics. Varying albumin affinity of the radiopharmaceuticals reveals changes in blood residence time,…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/87272
note: Use of Physiologically Based RadioPharmacoKinetic(PBRPK) Models to Simulate RadiopharmaceuticalTherapiesbyAli Fele-ParanjBSc in physics, Sharif University of Technology, 2021A THESIS SUBMITTED IN PARTIAL FULFILLMENTOF THE REQUIREMENTS FOR THE DEGREE OFMaster of Applied ScienceinTHE FACULTY OF GRADUATE AND POSTDOCTORALSTUDIES(Biomedical Engineering)The University of British Columbia(Vancouver)December 2023© Ali Fele-Paranj, 2023The following individuals certify that they have read, and recommend to the Fac-ulty of Graduate and Postdoctoral Studies for acceptance, the thesis entitled:Use of Physiologically Based RadioPharmacoKinetic (PBRPK) Modelsto Simulate Radiopharmaceutical Therapiessubmitted by Ali Fele-Paranj in partial fulfillment of the requirements for the de-gree of Master of Applied Science in Biomedical Engineering.Examining Committee:Arman Rahmim, Professor, Radiology and Physics, UBCSupervisorCarlos Uribe, Clinical Assistant Professor, Radiology, UBCSupervisory Committee MemberRoger Tam, Associate Professor, Biomedical Engineering, UBCSupervisory Committee MemberiiAbstractIn this thesis, we developed a computational framework using physiologicallybased pharmacokinetic (PBPK) models to study radiopharmaceutical kinetics inthe body. To handle the complexity of PBPK models (over 100 differential equa-tions), a scalable modeling notation called the ”reaction graph” is introduced.Implemented in Matlab’s Simbiology module and shared in the systems biologymarkup language (SBML) format, this notation enables easy model reproduction.Referred to as the physiologically based radiopharmacokinetic model (PBRPK), itis fine-tuned specifically for radiopharmaceuticals.Using the PBRPK model and literature-based parameters, we addressed threekey questions in radiopharmaceutical therapy. First, we systematically studied theinteraction between hot and cold species and its impact on absorbed dose in tumorsand organs at risk (OARs) and we found out that tumor receptor density…
has type: Thesis/Dissertation
date issued: 2023-11
is shown at: 10.14288/1.0438697
language: eng
degree discipline: Biomedical Engineering
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nd/4.0/
scholar level: Graduate
contributor: Rahmim, Arman
type: Text
identifier URI: http://hdl.handle.net/2429/87272