Towu-Aghantse, Emmanuel;
(2001)
Assessment of the uptake of Lipiodol and its conjugates by paediatric embryonal tumours.
Doctoral thesis (M.D.), University College London.
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Abstract
The uptake of Lipiodol, an iodinated poppy seed oil, by liver tumours has been utilised as a means of targeted therapy for advanced hepatocellular carcinoma in adults, and recently for hepatoblastoma in children with good palliation and conversion to operability. Liver tumours selectively retain Lipiodol for prolonged periods compared with non-tumorous tissue. It is uncertain, whether Lipiodol actually increases the concentration of the cytotoxics delivered into the liver tumours. This study evaluated these effects by quantifying the cellular fluorescence and localisation of Lipiodol-conjugates in hepatoblastoma, hepatocellular carcinoma, and a control cell line of human normal hepatocytes. Confocal Laser scanning microscopy revealed that the uptake of Lipiodol-doxorubicin and epirubicin conjugates by hepatoblastoma cell lines is predominantly into the nuclei. Lipiodol significantly increased both uptake and cytotoxicity in the tumour cell lines. In contrast epirubicin is localised in the cytoplasm of hepatocellular carcinoma cells, and neither its uptake nor its cytotoxicity is enhanced when administered with Lipiodol. The uptake of Radioactive Lipiodol I125 and Lipiodol 1125 was uniform in the cell lines studied, irrespective of whether single agents or the 'cocktail' of both radioactive agents was used. However clonogenic assay confirmed a much significantly higher cytotoxic effect by the 'cocktail' on the tumour cells. These findings suggest that a combination of Lipiodol I131 and Lipiodol 1125 may be more effective in treating patients with liver tumours. Neuroblastoma and nephroblastoma cells were also studied by exposing the respective cell lines to lipiodol. This revealed a cytoplasmic and intranuclear uptake by neuroblastoma, but not by nephroblastoma cells. These findings need further studies to explore a possible role for lipiodol-targeted therapy in children with advanced primary or metastatic neuroblastoma. It is concluded that lipiodol-conjugates may enhance the cytotoxicity of agents used in the treatment of pediatric embryonal tumours.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | M.D. |
| Title: | Assessment of the uptake of Lipiodol and its conjugates by paediatric embryonal tumours. |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis Digitised by Proquest. |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10121447 |
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