Auger electron radionuclide therapy utilising F3 peptide to target the nucleolus
<p>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 t...
| Main Author: | |
|---|---|
| Other Authors: | |
| Format: | Thesis |
| Language: | English |
| Published: |
2015
|
| Subjects: |
| _version_ | 1826316482699591680 |
|---|---|
| author | Hillyar, C |
| author2 | Vallis, K |
| author_facet | Vallis, K Hillyar, C |
| author_sort | Hillyar, C |
| collection | OXFORD |
| description | <p>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. <sup>111</sup>In-labelled F3 (<sup>111</sup>In-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. <sup>111</sup>In-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 <sup>111</sup>In-DTPA-F3 in the nucleus. The induction of γH2AX foci by <sup>111</sup>In-DTPA-F3 was found to be determined by the volume of the nucleolus. In conclusion, <sup>111</sup>In-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.</p> |
| first_indexed | 2024-03-06T21:27:58Z |
| format | Thesis |
| id | oxford-uuid:43bb1e8a-6f52-4eac-b742-0a988562e7fc |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-12-09T03:45:54Z |
| publishDate | 2015 |
| record_format | dspace |
| spelling | oxford-uuid:43bb1e8a-6f52-4eac-b742-0a988562e7fc2024-12-07T17:49:38ZAuger electron radionuclide therapy utilising F3 peptide to target the nucleolusThesishttp://purl.org/coar/resource_type/c_db06uuid:43bb1e8a-6f52-4eac-b742-0a988562e7fcRadiobiologyEnglishORA Deposit2015Hillyar, CVallis, KCornelissen, B<p>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. <sup>111</sup>In-labelled F3 (<sup>111</sup>In-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. <sup>111</sup>In-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 <sup>111</sup>In-DTPA-F3 in the nucleus. The induction of γH2AX foci by <sup>111</sup>In-DTPA-F3 was found to be determined by the volume of the nucleolus. In conclusion, <sup>111</sup>In-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.</p> |
| spellingShingle | Radiobiology Hillyar, C Auger electron radionuclide therapy utilising F3 peptide to target the nucleolus |
| title | Auger electron radionuclide therapy utilising F3 peptide to target the nucleolus |
| title_full | Auger electron radionuclide therapy utilising F3 peptide to target the nucleolus |
| title_fullStr | Auger electron radionuclide therapy utilising F3 peptide to target the nucleolus |
| title_full_unstemmed | Auger electron radionuclide therapy utilising F3 peptide to target the nucleolus |
| title_short | Auger electron radionuclide therapy utilising F3 peptide to target the nucleolus |
| title_sort | auger electron radionuclide therapy utilising f3 peptide to target the nucleolus |
| topic | Radiobiology |
| work_keys_str_mv | AT hillyarc augerelectronradionuclidetherapyutilisingf3peptidetotargetthenucleolus |