Thesis Format
Monograph
Degree
Master of Science
Program
Chemistry
Collaborative Specialization
Molecular Imaging
Supervisor
Luyt, Leonard G.
Abstract
The ghrelin receptor, crucial for regulating physiological processes and associated with various diseases, is a prime target for molecular imaging. Positron emission tomography (PET) imaging, known for its high sensitivity and non-invasive nature, has seen significant advancements. A potential PET radiotracer for the ghrelin receptor is a quinazolinone derivative with the highest reported ghrelin receptor binding affinity (IC50 = 20 pM) and favorable hydrophilicity (cLogD = 2.4). Previous attempts by Hou et al. and Childs to radiolabel this compound with fluorine-18 using nitro and spiroiodonium ylide precursors were unsuccessful. This thesis explores a novel approach using copper-mediated radiofluorination of a boronic ester precursor, though challenges arose in developing the precursor. Detailed are the issues faced during the multi-step synthesis, along with optimized reaction conditions and purification methods. This work provides guidance for future researchers in developing the PET radiotracer using copper-mediated radiofluorination and includes additional supporting data.
Summary for Lay Audience
The ghrelin receptor is an important target for diagnosing various diseases due to its involvement in critical physiological processes. One promising approach to leverage the ghrelin receptor for disease diagnosis is by developing a radiotracer that specifically binds to it. A radiotracer is a radioactive molecule that emits radiation and is detectable by specialized equipment, enabling clinicians to create detailed images of the body. These images can help diagnose diseases by highlighting areas where the radiotracer has accumulated, often indicating disease-related changes.
There are two main types of imaging techniques using radiotracers: SPECT and PET. PET imaging is generally preferred because it provides higher-quality images and involves isotopes that pose less risk to patients. Although several radiotracers targeting the ghrelin receptor have been developed for both SPECT and PET, none have shown exceptional performance in biological evaluations. Therefore, developing new and more effective radiotracers is crucial for advancing diagnostic capabilities.
This thesis explores the development of a potential PET radiotracer targeting the ghrelin receptor. The process involves incorporating radioactive isotopes into a molecule, a challenging task that requires advanced techniques in synthetic organic chemistry and radiochemistry. Though the desired outcome was not achieved, the research provides valuable data and insights. The lessons learned and the optimizations made during this process will guide future efforts in developing effective PET radiotracers that could eventually be used in clinical settings to improve disease diagnosis.
Recommended Citation
Al-Jaberi, Husain, "Attempt to Synthesize a Quinazolinone Aryl Boronic Ester Derivative for 18F-labeling and Positron Emission Tomography Imaging of the Ghrelin Receptor" (2024). Electronic Thesis and Dissertation Repository. 10552.
https://ir.lib.uwo.ca/etd/10552