Dissertations, Theses, and Capstone Projects

Date of Degree

6-2022

Document Type

Dissertation

Degree Name

Ph.D.

Program

Chemistry

Advisor

Stephen O'Brien

Advisor

Jan Grimm

Committee Members

Vinod Menon

Lynn Francesconi

Subject Categories

Biotechnology | Diagnosis | Materials Chemistry | Nanomedicine | Radiochemistry

Keywords

Cherenkov imaging, molecular imaging, nanoparticle, lanthanide material

Abstract

Cancer is a significant public health problem worldwide and is the second leading cause of death in the United States. Imaging has increasingly been used over the last two decades to improve the diagnosis and guidance of tumor tissue removal surgery. Among the most widely used techniques for in vivo imaging are planar and tomographic fluorescence imaging and bioluminescence imaging. Despite their utility, these techniques are primarily restricted to preclinical use. Factors that have prevented translation from the bench to the bedside include depth-penetration considerations, regulatory issues, and toxicity. A recent development in nuclear imaging has been the ability to visualize a decay signal of a Positron emission tomography (PET) radioisotope utilizing a cooled and highly sensitive CCD (Charge-coupled device) camera. This optical decay signal is Cerenkov Radiation, which provides a much faster imaging speed with lower service costs. Cerenkov imaging provides an opportunity to bridge the optical (preclinical) and nuclear (clinical) gap using approved tracers and therapeutic agents. Unfortunately, Cerenkov luminescence (CL) is a relatively weak event arising from radioactive decay, so a contrast agent to increase the Cerenkov light intensity without increasing the dose of radioactivity is urgently needed. This project is focused on the utilization of lanthanide nanoparticles, gold nanoclusters, and molecular gels, and to redshift the blue Cerenkov light to more the penetrative red-light region which is an in-directly way for Cerenkov enhancement. Meanwhile, a preliminary study of the potential of hyperbolic or plasmonic metamaterials could be developed at the nanoscale to be a discrete, three-dimensional object (a nanoparticle) that, when coupled to a CL emitter and rendered biocompatible, could become a powerful biomarker for in vivo imaging and disease detection. The enhancement strategy development will enable the facile imaging of radiotracer distribution for various useful biomedical and preclinical applications using optical imaging equipment. Applications using common and experimental PET and therapeutic radiopharmaceuticals have the potential to accelerate preclinical nuclear research. Cerenkov imaging is a relatively minority research area but has tremendous clinic potential since it uses the FDA-approved PET radiotracer.

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