Master of Science
The discovery of peptide-based targeted imaging agents is hindered by the required addition of a radionuclide that can affect the binding properties of the peptide. Screening of peptide libraries is problematic because they do not take into account the presence of the imaging agent. Herein the development of an organometallic OBOC peptide library that contain a rhenium (I) tricarbonyl-based imaging entity surrogate incorporated directly onto the peptide chain, is reported. Additionally, MALDI tandem mass spectrometry is reported as a method to deconvolute organometallic peptides containing four different rhenium (I) tricarbonyl chelates on the N-terminus of octapeptides. Furthermore, an organometallic OBOC peptide library is created and screened against the GLP-1R (glucagon-like peptide 1 receptor) in order to discover potential imaging agents for diagnosis of diabetes and insulinomas. The methods reported herein can be applied to develop peptide-based imaging agents for a wide variety of relevant targets.
Cruickshank, Dana R., "The Development of Organometallic OBOC Peptide Libraries for use in Molecular Imaging" (2012). University of Western Ontario - Electronic Thesis and Dissertation Repository. Paper 706.