DOI
https://doi.org/10.25772/214F-6988
Author ORCID Identifier
Defense Date
2018
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Mechanical and Nuclear Engineering
First Advisor
Jessika V. Rojas
Second Advisor
Reza Mohammadi
Third Advisor
Massimo F. Bertino
Fourth Advisor
Supathorn Phongikaroon
Fifth Advisor
Christina Tang
Abstract
Lanthanide phosphate (LnPO4) and lanthanide vanadate (LnVO4) nanoparticles (NPs) are promising platforms for theranostic applications because of their chemical stability, low solubility, low toxicity, and unique luminescence and magnetic properties. Motivated by the high radiation resistance and ability to host actinides of naturally occurring lanthanide-based compounds, LnPO4 and LnVO4 NPs were studied as radionuclide carriers for targeted radionuclide therapy using in vivoα-generators, 223Ra, 225Ac, and 227Th. The implementation of these radionuclides has shown potential for the treatment of micrometastases and solid tumors as well as challenges in the retention of decay daughters at the target site to minimize unwanted radiotoxicity. LnPO4 and LnVO4 core-shell NPs doped with either 156Eu, a “cocktail” of 85, 89Sr and 156Eu, or in vivo α-generators 223Ra, 225Ac, and 227Th were synthesized in aqueous media. In vitro retention of radionuclides was investigated by dialyzing the radionuclide-doped NPs suspensions against deionized water and quantifying the activity in dialysate aliquots over time. The crystal structure, morphology, physical stability, luminescence and magnetic properties were evaluated. Partial retention of 156Eu (~70–95%) and 85, 89Sr (>80%) was evidenced in LnPO4 core NPs, while 227Th and decay daughters were quantitatively retained in LaPO4 core + 2 shells NPs (>99%). Gd0.8Eu0.2VO4 and GdVO4 core-shell NPs showed partial retention of 223Ra (~75%), 225Ac (75–95%), 227Th (>96%), and decay daughters. Radionuclide retention was influenced by the lanthanide concentration, crystal structure, and number of shells. The partial retention of radionuclides in both LnPO4 and LnVO4 core-shell NPs may enhance the treatment efficacy while minimizing unwanted toxicity. LnVO4 core and core-shell NPs have potential as carriers of short-lived radionuclides for both diagnostic and therapeutic applications. Emission intensities were higher for LnVO4 with respect to LnPO4 NPs, whereas no significant difference was observed in the magnetic susceptibilities. GdVO4 core NPs displayed enhancement of the signal intensity in T1-weighted images. This work evidences the promising application of both LnPO4 and LnVO4 NPs as platforms for targeted radionuclide therapy and multimodal molecular imaging.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
12-4-2018