Development of a multimodal imaging probe for detecting aggressive prostate cancer

Clarke, Mitchell Thomas

Abstract

This thesis reports on the synthesis, development and validation of a novel, non-toxic dual modal bio-imaging probe that targets a conformational molecular switch and relocalisation of cell surface Endo180 into endosomes that occurs during the early stages of aggressive prostate cancer.
InP/ZnS quantum dots were synthesised using a successive heating methodology following the introduction of a cooling phase between the addition of ‘shelling’ precursors. Photoluminescent quantum yields following the synthesis of InP/ZnS (2) quantum dots are reported at 85.30% in hexane and 57% in water (following phase transfer).
An OI/MR dual-modal imaging probe was successfully synthesised following the surface modification of InP/ZnS (2) – TGA with Ln(III) DOTA chelate derivative (Ln = Gd, Eu and Tb). Up to 190 Gd(III) chelates were added to the surface of InP/ZnS (2) – TGA resulting in a combined r1 value of 1609.94 mM-1s-1 (InP/ZnS (2) – Gd.5a) when InP/ZnS (2) is synthesised with InI3. High values of photoluminescent quantum yield were achieved of up to 19.9% (InP/ZnS (2) – Gd.5.b) with no shift in emission properties observed following surface functionalisation when compared to InP/ZnS (2) – TGA.
A targeted dual modal OI/MR imaging probe for the early detection of aggressive prostate cancer has been developed, via a two-step surface modification of InP/ZnS (2) – TGA with Endo180 conformational specific antibodies (A5.158, 39.10) and Gd(III) chelate (Gd.5a).
Work presented in chapter 2 has formed part of the publication, Clarke, M. T.; Viscomi, N.; Chamberlain, T. W.; Hondow, N.; Adawi, A. M.; Sturge, J.; Erwin, S. C.; Bouillard, J.-S. G.; Tamang, S.; Stasiuk, G. J. Near Unity Quantum Yield in InP Based Quantum Dots through Thermal Diffusion. Commun. Chem. 2019, 2.

Citation

Clarke, M. T. Development of a multimodal imaging probe for detecting aggressive prostate cancer. (Thesis). University of Hull. https://hull-repository.worktribe.com/output/4223251

• Thesis Type: Thesis
• Deposit Date: Jul 8, 2021
• Publicly Available Date: Feb 23, 2023
• Keywords: Biomedical sciences
• Public URL: https://hull-repository.worktribe.com/output/4223251
• Additional Information: Department of Biomedical Sciences, The University of Hull
• Award Date: Mar 1, 2020