<p>The optimal way to detect and treat cancer is to target cancer cells exclusively without affecting the surrounding tissue. One promising approach is to use radiolabelled molecules to target receptors that are overexpressed in cancer cells. Since the epidermal growth factor receptor (EGFR) family is overexpressed in many types of cancer, it is an attractive target for both diagnostic and therapeutic applications.</p><p>This thesis can be divided into two parts. In part one (paper I), studies were conducted to modulate radionuclide uptake in tumour cells. The results showed that it was possible to modulate the cellular uptake of <sup>125</sup>I delivered by trastuzumab (targeting HER2) by adding EGF (targeting EGFR).</p><p>In part two (papers II-V) a high affinity EGFR-targeting affibody molecule (Z<sub>EGFR:955</sub>)<sub>2</sub> was selected and analysed both <i>in vitro</i> and <i>in vivo</i>. In papers II, III and V, the results obtained when using (Z<sub>EGFR:955</sub>)<sub>2</sub> were compared with those obtained with the two EGFR-binding molecules, EGF and cetuximab. These studies demonstrated that the affibody molecule bound specifically to EGFR (probably to subdomain III) with high affinity (~50 nM in biosensor analysis and ~1 nM in cellular studies) and produced intracellular signalling changes similar to those with cetuximab. In paper IV, <i>in vivo</i> studies were made, demonstrating that [<sup>111</sup>In](Z<sub>EGFR:955</sub>)<sub>2</sub> gave a tumour-specific <sup>111</sup>In uptake of 3.8±1.4% of injected dose per gram tumour tissue, 4 h post-injection. The tumours could be easily visualized with a gamma camera at this time-point. </p><p>The results of these studies indicated that the affibody molecule (Z<sub>EGFR:955</sub>)<sub>2</sub> is a possible candidate for radionuclide-based imaging of EGFR-expressing tumours. The biological effects of (Z<sub>EGFR:955</sub>)<sub>2</sub> might be of interest for therapy applications.</p>
| Identifer | oai:union.ndltd.org:UPSALLA/oai:DiVA.org:uu-8721 |
| Date | January 2008 |
| Creators | Nordberg, Erika |
| Publisher | Uppsala University, Biomedical Radiation Sciences, Uppsala : Acta Universitatis Upsaliensis |
| Source Sets | DiVA Archive at Upsalla University |
| Language | English |
| Detected Language | English |
| Type | Doctoral thesis, comprehensive summary, text |
| Relation | Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 1651-6206 ; 350 |
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