<p>Targeted radiotherapy (TRT) of cancer is a promising approach that enables selective treatment of tumour cells, while sparing normal tissue. The humanized monoclonal antibody A33 (huA33) is a potential targeting agent for TRT of colorectal cancer, since its antigen is expressed in more than 95 % of all colorectal carcinomas. The aim of this thesis was to evaluate the therapeutic potential of the two huA33-based TRT-conjugates, <sup>177</sup>Lu-huA33, and <sup>211</sup>At-huA33.</p><p>The conjugates <sup>177</sup>Lu-huA33, and <sup>211</sup>At-huA33, bound specifically to colorectal cancer cells, both <i>in vitro</i> and <i>in vivo</i>. A dose dependent cytotoxic effect of <sup>211</sup>At-huA33 was also demonstrated <i>in vitro</i>. From a therapeutic perspective, both conjugates had a favourable biodistribution in tumour-bearing nude mice, with high tumour uptake and a low uptake in normal organs (with the exception of an expected thyroid uptake of <sup>211</sup>At). After injection of <sup>211</sup>At-huA33, the blood absorbed a slightly higher dose than the tumour, but for <sup>177</sup>Lu-huA33, the tumour received a 12 times higher dose than blood. Two days after intravenous injection of <sup>177</sup>Lu-huA33 in tumour-bearing mice, the tumours could be clearly visualised by gamma camera imaging, with very low interference from normal tissue radioactivity. In an experimental therapy study, also performed in tumour-bearing mice, there was an excellent therapeutic effect of <sup>177</sup>Lu-huA33. About 50 % of the treated animals were tumour free 140 days after injection of <sup>177</sup>Lu-huA33, while none of the non-radioactive controls survived beyond 20 days after injection of treatment substances.</p><p>In conclusion, this thesis demonstrates that the therapeutic conjugates <sup>177</sup>Lu-huA33, and <sup>211</sup>At-huA33, are promising targeting agents that might help improve therapy of colorectal cancer.</p>
| Identifer | oai:union.ndltd.org:UPSALLA/oai:DiVA.org:uu-8657 |
| Date | January 2008 |
| Creators | Almqvist, Ylva |
| Publisher | Uppsala University, Radiology, 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 ; 336 |
Page generated in 0.0023 seconds