Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.713948
Title: Auger electron radionuclide therapy utilising F3 peptide to target the nucleolus
Author: Hillyar, Christopher
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2015
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Abstract:
F3 is a 31 amino acid peptide that possesses tumour homing capability and binds to nucleolin (NCL) expressed on the cell surface of malignant cells. Exposure of osteosarcoma (U2OS) cells to F3 peptide was found to shift the distribution of NCL and nucleophosmin (NPM) from the nucleolus to the nucleoplasm, and increase the level of Ki-67 in the nucleoplasm. 111In-labelled F3 (111In-DTPA-F3) was successfully radiosynthesised and was found to be significantly radiotoxic to MCF7, HCT116, MDA-MB-231/H2N, H322 and MDA-MB-435 cells, but not U2OS cells. 111In-DTPA-F3 was shown to be taken up, and to deposit radiation dose, in the nucleolus. The level of cell kill produced by 111In-DTPA-F3 was highly variable (19 fold range in surviving fraction) depending on the malignant cell line, and was correlated with the localisation of cell-bound 111In-DTPA-F3 in the nucleus. The induction of ?H2AX foci by 111In-DTPA-F3 was found to be determined by the volume of the nucleolus. In conclusion, 111In-DTPA-F3 is a promising Auger electron-emitting radiotherapeutic agent that targets the nucleolus, the radiosensitivity of which may vary depending on the malignant cell line.
Supervisor: Vallis, Katherine ; Cornelissen, Bart Sponsor: Medical Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.713948  DOI: Not available
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