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Appendix: Supplementary Material: Experimental details for unpublished work described in the thesis
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
Manuscript (Other academic)
URN: urn:nbn:se:uu:diva-89747OAI: oai:DiVA.org:uu-89747DiVA: diva2:161476
Available from: 2002-04-03 Created: 2002-04-03 Last updated: 2010-01-13Bibliographically approved
In thesis
1. On the Use of 76Br-labelled Monoclonal Antibodies for PET: Preclinical Evaluation of Halogenated Antibodies for Diagnosis and Treatment of Cancer
Open this publication in new window or tab >>On the Use of 76Br-labelled Monoclonal Antibodies for PET: Preclinical Evaluation of Halogenated Antibodies for Diagnosis and Treatment of Cancer
2002 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Radioactive substances are used in vivo to localize and characterize malignant tumours, generally by scintigraphic methods. In this context positron emission tomography (PET) in combination with radiolabelled monoclonal antibodies (mAbs) may provide a sensitive and specific method for detection of cancer. Individual dose calculations, based on such PET measurements, may be carried out to predict the possible use of mAbs labelled with therapeutic nuclides. The positron emitter 76Br, with a half-life of 16 h, is a well-suited candidate for radiolabelling and PET imaging. One drawback of radiobromine is that bromide, the ultimate catabolite after degradation of brominated mAb, is only tardily excreted from the body and is evenly distributed throughout the extracellular space, thereby increasing the background radioactivity. The aim of this work was to produce 76Br-mAb preparations with high accumulation and retention in tumour tissue together with a quick clearance of 76Br-labelled catabolites. Furthermore, the possibility to use brominated or iodinated mAbs in combination with PET to predict 211At-mAb dosimetry was evaluated.

Monoclonal Abs directed against colorectal cancer were labelled with 76Br using the direct Chloramine-T-method or indirectly by labelling the precursor molecule N-succinimidyl para-(tri-methylstannyl) benzoate with 76Br, which was subsequently conjugated to the mAbs. Monoclonal Ab A33 labelled with 76Br using the two labelling protocols was characterized in vitro and in vivo in a rat tumour xenograft model. The mAb A33 was also labelled with 125I for comparison. In addition, mAb A33 was labelled with 211At, 125I and 76Br using the indirect labelling protocol and the mAb pharmacokinetics was studied in normal rats in order to estimate if data from brominated or iodinated mAb could be used for dosimetry of 211At in healthy organs and tissue.

In conclusion, both direct and indirect labelling resulted in high yields and mAbs with preserved immunoreactivity. In vivo characterization of 76Br-brominated mAb A33 showed that the indirect labelling method makes 76Br-brominated mAb A33 a promising candidate for tumour imaging with PET due to the faster excretion of radiolabelled catabolites compared with direct bromination. Finally, mAb A33 labelled with 76Br and 124/125I can be used to predict the 211At dose of astatinated mAb A33 in most organs given that a correction factor is applied for organs with varying uptake.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2002. 64 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1128
Oncology, bromine-76, positron emission tomography, monoclonal antibodies, cancer, direct and indirect radiohalogenation, Onkologi
National Category
Cancer and Oncology
Research subject
urn:nbn:se:uu:diva-1908 (URN)91-554-5258-2 (ISBN)
Public defence
2002-04-27, Grönwaldsalen, Akademiska Sjukhuset, ing. 70, Uppsala, 13:15
Available from: 2002-04-03 Created: 2002-04-03Bibliographically approved

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