Advisory Committee Chair
Suzanne E Lapi
Advisory Committee Members
Thomas M Ryan
Date of Award
Degree Name by School
Doctor of Philosophy (PhD) School of Medicine
Positron Emission Tomography (PET) has revolutionized the world of molecular imaging, increasing the potential for improved diagnosis and characterization of various disease states, including cancer. Molecular biology has afforded the knowledge that each type of cancer cell is different, and these differences can be leveraged to develop methods for targeting these cells for imaging or therapy, as well as understanding of other characteristics. Due to the increased diversity in available targets, there has been an equal need to develop new agents used to image these receptors. Radioisotopes with varying halflives, chemical and nuclear properties have been studied in recent years to help satisfy these needs. Titanium-45 (t½ = 3.08 hours) is a radioisotope that was not widely studied due to difficulties in developing its aqueous radiochemistry, however, through this work it was determined that the challenges could be overcome. The nuclear properties of this radioisotope including its branching ratio (85%) and average positron energy (b+avg = 0.439 MeV), make it a desirable radionuclide in the field of molecular imaging. Due to these nuclear properties, we hypothesized that PET images acquired with 45Ti would be of high quality, and the 3-hour half-life would allow sufficient time for purification, chemistry, and in vivo analysis. iv Due to its minimal presence in the literature, we aimed to expand radiochemistry pertaining to 45Ti. This work showed that 45Ti could be conjugated in high radiochemical yields to the widely available chelator Deferoxamine (DFO) but would need to be accomplished at high pH levels. The radiochemistry to complete this conjugation was developed in this work, with high radiochemical yields. Furthermore, Prostate Specific Membrane Antigen (PSMA) was determined to be a desirable target in this work due to its over expression in almost all prostate cancers, and the clinical need to develop novel targeting probes for this receptor. Novel probes for the PSMA receptor were also determined to be effective in this work via conjugation of 2-[3- (1,3-dicarboxypropyl)ureido]pentanedoic acid (DUPA) to the DFO chelator and subsequent radiolabeling with 45Ti. 45Ti can be an excellent addition to the PET radiometal toolbox, and this work paves the way for future research.
Chaple, Ivis Francis, "Production and Purification of Titanium-45 for Imaging of PSMA+ Prostate Cancer" (2021). All ETDs from UAB. 619.