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Hydrazine Derivatives as a Platform for Site-Specific Labelling of Peptides for in vivo Molecular Imaging of Disease

Holland, Charlotte (2015) Hydrazine Derivatives as a Platform for Site-Specific Labelling of Peptides for in vivo Molecular Imaging of Disease. Master of Science by Research (MScRes) thesis, University of Kent.

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Abstract

The 6-hydrazinonicotinyl group, known as HYNIC, is an attractive bifunctional coupling agent for preparing 99mTc-labeled peptides and proteins for medical imaging. Peptides are useful for imaging disease states such as cancer and inflammation because they take advantage of a distinct cellular target, such as a receptor, being present on the cell. Receptors are often over expressed on tumour cells. Peptides will bind to their receptors with high specificity and affinity. There is a recognized need to create well-de?ned polymer probes for in vivo and clinical PET and SPECT imaging to guide the development of new generation polymer therapeutics. In general the amount of radionuclide used in radiopharmaceuticals is small, so attaching the radionuclide to a polymer ensures that the radionuclide will be highly concentrated in the radiopharmaceutical. The number of binding sites is increased with the copolymer making it a viable choice for radiolabelling applications. The chances of successfully imaging the point of interest are therefore increased.

This work also presents the synthesis of a bifunctional copolymer (POEGMA-co-PAMA) which is biocompatible and can be attached to a HYNIC group and subsequently a peptide. This copolymer was synthesised using a controlled living radical polymerisation technique called Reversible Addition Fragmentation chain Transfer (RAFT). This technique was chosen due to its ability to synthesise polymers with predetermined molecular weights of complex architectures whilst maintaining control over polydispersity. Copolymers of varying compositions were synthesised and analysed by GPC and NMR. This method (once optimised) would allow for the copolymer to be labelled with technetium-99 for SPECT, providing an alternative bioconjugate synthetic route.

Item Type: Thesis (Master of Science by Research (MScRes))
Thesis advisor: Biagini, Stefano C. G.
Uncontrolled keywords: radiolabel 6-HYNIC technetium-99 SPECT
Subjects: Q Science
Q Science > QD Chemistry
Divisions: Faculties > Sciences > School of Physical Sciences
Depositing User: Users 1 not found.
Date Deposited: 22 Sep 2015 13:00 UTC
Last Modified: 15 Jan 2020 04:07 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/50575 (The current URI for this page, for reference purposes)
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