ORCID

http://orcid.org/0000-0002-1321-0803

Date of Award

Winter 12-15-2018

Author's School

Graduate School of Arts and Sciences

Author's Department

Chemistry

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

Positron emission tomography (PET) imaging utilizes drugs labeled with positron emitters to target and evaluate different biological processes occurring in the body. Tailoring medicine to the individual allows for higher quality of care with better diagnosis and treatment and is a key purpose for advancing research into developing new platforms for PET imaging agents. A PET nuclide of high interest for the development of these agents is 89Zr. This can be attributed to the long half-life of 3.27 days and low positron energy of 89Zr.

In this work, we developed a production method for 89Zr using Y sputtered coins that is now in current use at the University of Alabama at Birmingham for both research and human-use studies. An alternative means of separation for 89Zr from Y using IDA as an eluant with inorganic resin obtained from Brookhaven National Laboratory was also investigated in order to develop a method that alleviated the necessity to remove the chelator before human injections. The low-level activity separations were reproducible with successful test labeling showing the potential this method has as an alternative separation method.

Although 89Zr has great potential as PET nuclide, it is a known bone seeker, meaning if it decomplexes from a chelator, it will be taken up in the bone. The natural affinity of 89Zr for bone can be exploited as a radiolabeling technique using nHAp. Nanoparticles composed of the main component in the bone matrix, nHAp, were used to exploit the natural affinity of 89Zr and other bone-seekers have for bone to develop a platform for PET imaging agents. The particles were easily labeled with high stability and little bone uptake in vivo. As a proof of concept that this could be used to develop targeted imaging agents, co-precipitated nHAp was rapidly modified with an analog of TOC to target SSTR2 receptors in AR42J cells to show specific targeting. Both the cells studies and the preliminary animal studies showed that there was specific targeting of the novel agents. Overall, the preliminary studies with 89Zr-nHAp-phospha-TOC are very promising for nHAp as a new platform for PET imaging agents.

Language

English (en)

Chair and Committee

Suzanne Kevin E. Lapi Moeller

Committee Members

Suzanne E. Lapi, Kevin Moeller, John R. Bleeke, Buck Rogers,

Comments

Permanent URL: https://doi.org/10.7936/42va-z537

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