Doctor of Philosophy (Ph.D.)
Degree Granting Department
Eduardo G. Moros, Ph.D.
Ghanim Ullah, Ph.D.
David L. Morse, Ph.D.
Mikalai M. Budzevich, Ph.D.
Monte Carlo, Radiation Detection, Radiation Dosimetry, radiopharmaceutical therapy
The use of targeted ligands to deliver radioisotopes directly to tumor cells is a promising therapeutic strategy. Because of the short path length and high LET of alpha particles, targeted alpha particles are ideal for treating metastatic disease while minimizing damage to non-targeted tissues. However, clinical methods for determining 3D radiation dosimetry in patients with multiple metastatic lesions are needed to support clinical translation of novel targeted alpha particle therapies for personalized treatment, especially in patients that have previously received radiotherapy. Recently interest in novel radiopharmaceutical development has grown significantly. However, compared to external beam radiation therapy, progress in customizing radiopharmaceutical treatments specific to the patient has remained stagnant for decades. Currently, therapies are given using fixed dose administrations and dosimetry is performed using outdated simplistic representations of a standard human. The potential benefits of targeted alpha therapies cannot be taken advantage of until pretreatment planning is employed to optimize each patient’s therapy on an individual basis. Dose response relationships need to be analyzed post-treatment to assess tumor control probabilities and normal tissue complications. With new developments in medical imaging and instrumentation, along with the continuously increasing computational power available, personalized targeted alpha therapies can be achieved.
In this work, a novel targeted alpha therapy for treatment of metastatic uveal melanoma, 225Ac-DOTA-MC1RL, is developed and thoroughly tested pre-clinically. The therapy showed rapid eradication of tumors with no normal tissue toxicity with a single administration. Radiation detection instrumentation is improved upon by developing a method to more accurately quantify radioactivity for administration, biodistribution, pharmacokinetics, and dosimetry. A voxel-based Monte Carlo dosimetry methodology is developed using a novel companion imaging agent in both phantom and in vivo pre-clinical imaging studies. From these studies, a clinically translatable workflow is described and tested. 3D dosimetry calculations were performed enabling volumetric dose analysis for the novel therapy.
Scholar Commons Citation
Tichacek, Christopher John, "Development of a Voxel-Based Monte Carlo Radiation Dosimetry Methodology for a Targeted Alpha Particle Therapy" (2019). Graduate Theses and Dissertations.