The incidence of urinary bladder carcinoma is increasing and many patients die every year of this disease despite assumed radical therapy. Thus, there is a need for improved methods of diagnosis and therapy. Radionuclide targeting is based on achieving specific delivery of radioactive nuclides to tumour cells with minimal damage to surrounding normal tissues. Two possible target structures are the epidermal growth factor (EGF) receptor and the related receptor HER-2. Cellular binding and retention of 125I-EGF-dextran conjugates was investigated in two bladder carcinoma cell lines. The conjugate bound specifically to the EGF receptor with delayed maximum binding, limited intracellular degradation and prolonged cellular retention compared to 125I-EGF. EGF was labelled using different radionuclides and methods. All the labelled variants bound specifically to the tumour cells although the cellular binding patterns and retention varied considerably. 111In-DTPA-EGF had highest cellular retention and in decreasing order 211At-benzoyl-EGF and 125I-labelled EGF. Bladder cancer spheroids bound both 125I-EGF-dextran as well as 125I-EGF. Conjugate binding increased during a 48 h incubation period and was most prominent in the outer cell layers. The length of the dextran chain appeared not to alter the binding pattern. The expression of EGF receptors and HER-2 in metastases and primary bladder carcinoma tumours was investigated. Both receptors were expressed in the majority of metastases and primary tumours. Targeting the EGF receptor and/or HER-2 in urinary bladder carcinoma is an exciting new concept.
| Identifer | oai:union.ndltd.org:UPSALLA1/oai:DiVA.org:uu-1097 |
| Date | January 2001 |
| Creators | Sjöström, Anna |
| Publisher | Uppsala universitet, Institutionen för onkologi, radiologi och klinisk immunologi, Uppsala : Acta Universitatis Upsaliensis |
| Source Sets | DiVA Archive at Upsalla University |
| Language | English |
| Detected Language | English |
| Type | Doctoral thesis, comprehensive summary, info:eu-repo/semantics/doctoralThesis, text |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 0282-7476 ; 1042 |
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