Date of Award
12-18-2024
Degree Name
Master of Science (MS)
Degree Type
Thesis
Abstract
Numerous candidate nuclides have been undergoing rigorous preclinical development in the pursuit of novel targeted therapies. Successful development of these drugs relies on the understanding of physiological impacts at the macro and micro scales, in addition to a scalable process for their production. Here, mathematical and computerized approaches have been developed to guide this preclinical development. In this report, two alpha emitting nuclides Pb-212 and Ra-223 are modeled. Radium-223 dichloride citrate a newly approved ion indicated for treatment of bone metastatic castrate resistant prostate cancer, irradiates lesions through targeted uptake in bone at sites of disease. We have undertaken the first Monte Carlo dosimetry studies of Radium-223 dose distribution based on primary patient-derived specimens. This extends from our work on high resolution autoradiography from patient-derived bone lesion biopsies and high-resolution micro-X-ray computed tomography (micro-CT). A set of four activity distributions were simulated on three patient bone lesion biopsy samples. These simulations validate the novel tool for micron-scale modeling with patient-derived specimens. Ablative dose profiles are shown to be driven by uptake distributions as well as the target tissues microstructure. Additionally, we demonstrate a mathematical model for a novel Pb-212 emanation (gas) generator. Via the Bateman equations, we optimized for maximal yield of Pb-212. Through Insilco experiments of the generator, a 1-minute syringe hold time was demonstrated to maximize yields over a twelve-hour experiment. The ingrowth of Pb-212 daughters was also successfully measured with the modeling of Bi ingrowth of time. Through the computerized modeling of Ra-223 treatment in addition to the modeling of Pb-212 production have outlined a novel and powerful methodology needed for the successful preclinical development of novel radiopharmaceuticals.
Language
English (en)
Chair
Daniel Thorek
Committee Members
Daniel Thorek, Abhinav Jha, Justin Mikell