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Therapy of colorectal cancer xenografts in nude mice using 177Lu labelled humanized antibody A33
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
Manuscript (Other academic)
Identifiers
URN: urn:nbn:se:uu:diva-97088OAI: oai:DiVA.org:uu-97088DiVA: diva2:171876
Available from: 2008-04-23 Created: 2008-04-23 Last updated: 2010-01-13Bibliographically approved
In thesis
1. Targeted Therapy of Colorectal Cancer: Preclinical Evaluation of a Radiolabelled Antibody
Open this publication in new window or tab >>Targeted Therapy of Colorectal Cancer: Preclinical Evaluation of a Radiolabelled Antibody
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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, 177Lu-huA33, and 211At-huA33.

The conjugates 177Lu-huA33, and 211At-huA33, bound specifically to colorectal cancer cells, both in vitro and in vivo. A dose dependent cytotoxic effect of 211At-huA33 was also demonstrated in vitro. 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 211At). After injection of 211At-huA33, the blood absorbed a slightly higher dose than the tumour, but for 177Lu-huA33, the tumour received a 12 times higher dose than blood. Two days after intravenous injection of 177Lu-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 177Lu-huA33. About 50 % of the treated animals were tumour free 140 days after injection of 177Lu-huA33, while none of the non-radioactive controls survived beyond 20 days after injection of treatment substances.

In conclusion, this thesis demonstrates that the therapeutic conjugates 177Lu-huA33, and 211At-huA33, are promising targeting agents that might help improve therapy of colorectal cancer.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2008. 54 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 336
Keyword
Molecular medicine, tumour targeting, antibody, A33, radionuclide, colorectal cancer, therapy, Molekylärmedicin
Identifiers
urn:nbn:se:uu:diva-8657 (URN)978-91-554-7171-2 (ISBN)
Public defence
2008-05-17, Rudbecksalen, Rudbecklaboratoriet, Dag Hammarskjölds väg 20, Uppsala, 09:15
Opponent
Supervisors
Available from: 2008-04-23 Created: 2008-04-23 Last updated: 2011-01-25Bibliographically approved

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