Dosimetry and Application of Magnetic Nanoparticles as an Intraocular Shielding Method in Iodine-125 Eye Plaque Brachytherapy

Abstract

Uveal melanoma is a rare diagnosis but the most common intraocular malignancy. Eye plaque brachytherapy has been the standard of care since the introduction of the Collaborative Ocular Melanoma Study (COMS), which proved excellent tumor control and survival for uveal melanoma patients. Despite these successes, normal tissues of the eye receive excessive dose during treatment that is historically unavoidable. The purpose of this work is to implement a novel intraocular shielding technique to reduce normal tissue dose while maintaining tumor control, using a magnetic plaque and ferromagnetic nanoparticles. The ferromagnetic nanoparticles studied have previously been used intraocularly for retinal detachment. A new application of ferromagnetic nanoparticles is studied. Previously literature has extensively studied outcomes and incidence rates of normal tissue complications for plaque brachytherapy patients, however a gap exists addressing what normal tissue dose is acceptable to avoid such complications. To answer this question, a retrospective study was conducted with uveal melanoma patients treated with COMS plaques. The conclusions can not only help predict normal tissue complication in the future, but also justify the amount of shielding necessary with magnetite nanoparticles. A proof-of-concept magnetic plaque was designed to guide ferromagnetic nanoparticles around the tumor, creating a shield for normal tissues. The distribution of ferrofluid was fully characterized with film and Monte Carlo (MC) methods to determine dose distribution throughout the eye. Using a novel film calibration technique, radiochromic film was calibrated using low energy Iodine-125. In addition, the MC-simulated source and COMS plaque were benchmarked to validate the source code and the accuracy of the modeled sources and plaque. In this work the retrospective study is presented followed by film and MC measured dose distribution in the eye with ferromagnetic nanoparticle shielding. Lastly, the fluid flow and fluid distribution are simulated with multiphysics software. The results can be clinically applied to establish how much shielding is necessary to prevent normal tissue toxicity, and what magnitude of dose reduction is feasible based on the presented proof-of-concept design. A supplementary video file shows the fluid flowing against gravity, toward the custom magnetic plaque, distributing around a 5 mm tumor. The video enhances the content and figures introduced in Chapter 5.