Radiochemistry Commons^™

The Development Of Novel Radioimmunoconjugates For The Pet Imaging And Radioimmunotherapy Of Cancer, Samantha M. Sarrett

Dissertations, Theses, and Capstone Projects

Antibodies have long played a vital role in nuclear medicine for both the diagnosis and therapy of various malignancies. The role and development of antibodies in nuclear medicine can be broadly separated into three different categories: 1) bioconjugation strategies, 2) immunoPET imaging, and 3) radioimmunotherapy. This dissertation will attempt to comprehensively cover each of these categories through a series of studies, protocols, and reviews. For the bioconjugation strategies, we will describe the development of a novel site-selective bioconjugation strategy using an innovative lysine-targeting reagent, PFP-bisN₃, to prepare [⁸⁹Zr]Zr-^SSKDFO-pertuzumab for visualizing HER2+ breast cancer. Further, …

The Reduction, Sequestration, And/Or Coordination Of Technetium-99 Utilizing Polyoxometalates And Nanomaterials, Colleen Mb Gallagher

Dissertations, Theses, and Capstone Projects

Research into the sequestration of radionuclides from aqueous media is being conducted due to the contamination of aqueous waste effluents and groundwater with highly toxic long-lived radionuclides. These contaminants are introduced into water and streams from legacy nuclear sites, nuclear reactor operations, nuclear fuel reprocessing, nuclear weapons testing, and plutonium production. A major contributor (~6%) to the waste from thermal neutron fission of uranium-235 is the radionuclide technetium-99 (⁹⁹Tc). It is considered a long-lived radioisotope with a half-life of 2.1x10⁵ years. It is a weak beta emitter with a max energy of 0.29 MeV and is most …

Leveraging Antibodies For Positron Emission Tomography And Near-Infrared Fluorescence Imaging Of Cancer, Kimberly C. Fung

Dissertations, Theses, and Capstone Projects

The high specificity and affinity of antibodies make them attractive for developing drugs to diagnose and treat cancer. The overarching goal of this work is to explore the synthesis and use of antibody-based imaging agents in preclinical models of cancer. This work can be described as two-fold. In the first part, we investigated how the use of a glycans-specific bioconjugation strategy affects Fc gamma RI binding and why it results in improved in vivo performance of immunoconjugates. To do so, we used the clinically relevant positron emission tomography (PET) imaging agent, ⁸⁹Zr-DFO-pertuzumab, in mouse models of human breast cancer. …

A Pretargeted Spect Imaging Strategy Employing Technetium-99m Based On Bioorthogonal Diels-Alder Click Chemistry, Justin H. Walsh

Dissertations, Theses, and Capstone Projects

A series of related N₃S ^99mTc-peptide complexes were synthesized and tested for use in pretargeting SPECT imaging that utilizes the bioorthogonal Diels-Alder click reaction between tetrazine (Tz) and transcyclooctene (TCO). The objective was to optimize the excretory pathways of the ^99mTc-peptide complexes for maximum tumor targeting with the in vivo “click” and minimum non-target uptake. The ^99mTc–tetrazine constructs were prepared by reaction of ^99mTc-peptide complexes (^99mTc-FKC, ^99mTc-FKCR, ^99mTc-DKC, and ^99mTc-SKC) with Tz-NHS or Tz-PEG₅-NHS to form ^99mTc FK(Tz)C, ^99mTc-FK(PEG₅-Tz)CR, ^99mTc-DK(PEG₅-Tz)C, …

Synthesis And Evaluation Of Novel Iodine-124 Labeled Nucleoside Analogs As Pet Imaging Agents To Predict Response To Gemcitabine Therapy, Kishore Kumar Gangangari

Dissertations, Theses, and Capstone Projects

Gemcitabine (gem) is a nucleoside analog that is used to treat pancreatic cancers (PaCa), which have dismal prognosis and low survival rate. Though gem is used as first line of treatment for PaCa, the response rate is quite low (~30%). Currently, there is no a priori way to determine a responder from a non-responder to gem therapy either invasively or non-invasively. Any biomarker that can act as a prognostic indicator of gem response will greatly aid in selecting responsive patients to gem therapy and provide alternative options such as Folfirinox or other treatments to resistant patient population. Amongst various known …

Pretargeted Radioimmunotherapy Utilizing The Inverse Electron Demand Diels-Alder Reaction, Rosemery Membreno

Dissertations, Theses, and Capstone Projects

Radioimmunotherapy capitalizes on the specificity and affinity of antibodies for their antigens to localize radioactivity at the tumor site. One limitation in using antibodies is their long circulation time, which can take days to weeks to fully clear from blood circulation. When a radioisotope is directly conjugated to this immunoglobulin vector, the red marrow and other healthy organs are receiving a constant radiation dose while it is in blood circulation. This not only harms healthy organs, but limits the dose of radioactivity that can be administered thus prolonging treatment. A promising alternative to limit the radiation dose to non-tumor tissue …

The Development Of Novel Platforms For The Imaging Of Cancer By Positron Emission Tomography, Brendon E. Cook

Dissertations, Theses, and Capstone Projects

The role of antibody-based imaging of cancer by positron emission tomography (PET) has expanded significantly in recent years and is poised to radically alter the way that cancer is diagnosed and treated. However, one hurdle that remains is the potentially harmful radiation dose that comes from these imaging agents, as the long circulation time of antibodies (days to weeks) necessitates the use of radionuclides with comparable physical half-lives (i.e. ⁸⁹Zr, ¹²⁴I, etc.). One particularly promising solution is the use of the inverse electron demand Diels-Alder (IEDDA) reaction between a 1,2,4,5-tetrazine (Tz) and a trans-cyclooctene (TCO) for pretargeting. …

Fundamental Chemistry Related To The Separations And Coordination Of Actinium-225, Thorium-227, And Technetium-99, Jasmine L. Hatcher

Dissertations, Theses, and Capstone Projects

This work explores the fundamental chemistry of actinium, thorium, and technetium in an effort to develop methodologies which help to address complications specific to each of these elements. Developing fundamental knowledge in inorganic chemistry has the power to meaningfully address a number of real world problems. By using simple systems and experiments like following an electron or changing the solvent system, we are able to gain invaluable information which can be used to address major issues.

Actinium-225 (t_½: 9.92 d) is an alpha-emitting radionuclide with nuclear properties well suited for alpha therapy of malignant tumors. The present global …

Parp Pet Imaging Agents, Brandon Carney

Dissertations, Theses, and Capstone Projects

The poly (adenosine-diphosphate (ADP) ribose) polymerase (PARP) family of enzymes has been of interest to researchers and clinicians for over fifty years, especially the first member of the family, PARP1. This enzyme has become a target for cancer therapeutics due the reliance of highly proliferating cells on PARP1 for genomic maintenance. In the coming age of individualized medicine, however, highly specific therapeutic agents like PARP inhibitors are in need of similarly highly specific companion diagnostic agents. These kind of agents have been made possible with the quickly progressing field of molecular imaging. Specifically, positron emission tomography (PET) has enabled the …

Chelating Ligands And Nanomaterials Based On Graphene Oxide For The Reduction And Sequestration Of Radiometals And Protein Purification, Sam Groveman

Dissertations, Theses, and Capstone Projects

Nuclear waste remediation and protein purification using immobilized metals can benefit enormously from the design and implementation of novel chelating nanomaterials. Available commercial resins capable of sequestering metals are based on bulk materials such as organic polymers, ceramics, and their composites. The use of two-dimensional nanoplatforms with large surface areas expands the horizon for the research and development of new systems with higher efficiency and lower cost. Fundamental science challenges remain in the synthesis and characterization of these nanomaterials and their integration with known or novel coordinating ligands.

Chemical exfoliation of graphite under strong oxidizing conditions yields graphene oxide (GO) …

Development Of New Radiolabeling Methods And Insights On Ionizing Radiation Interactions With Nanoparticles, Travis Shaffer

Dissertations, Theses, and Capstone Projects

Nanoparticles are often combined with radionuclides for various applications, ranging from waste remediation to imaging and therapy in the medical field. The overarching aim of this body of work is two-fold. The first aim is development of new radiolabeling methods for various nanoparticles that allow stable attachment of a variety of imaging and therapeutic radionuclides. The second portion more fully describes mechanisms of interaction between ionizing radiation and nanoparticles.

The following advancements will be presented in this dissertation: i) a new radiolabeling method for silica and silica-based nanoparticles that does not require the use of specific chelators, with both radiochemical …

Design Rules For The Nucleation, Growth, And Encapsulation Of Gold Nanoparticles With Applications To Cancer Imaging, Matthew A. Wall

Dissertations, Theses, and Capstone Projects

Surface-enhanced Raman scattering (SERS) nanoparticles are exciting candidates for high-precision cancer imaging due to their highly specific spectral signature (Raman “fingerprint”) and propensity for passive targeting of cancerous tissues. However, the signal intensity of currently available SERS nanoparticles is insufficient for cancer imaging via passive targeting in most solid tumors. The overarching aim of this body of work is to develop a new generation of SERS nanoparticles with sufficiently low limits of detection to enable robust detection of various solid tumors in vivo.

The complexity of SERS nanoparticles requires significant advances to the theoretical and experimental understanding of metal …