Use of Physiologically Based Radiopharmacokinetic (PBRPK) Models to Simulate Radiopharmaceutical Therapies

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.