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Polyhedral boron clasters as linkers for attachment of radiohalogens to tumor targeting proteins. II. Radioiodination of monoclonal antibody using potassium [125I]-4-(isothiocyanatobenzylammonio)-iodo-decahydro-closo-dodecaborate (Iodo-DABI)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.ORCID iD: 0000-0001-6120-2683
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URN: urn:nbn:se:uu:diva-90197OAI: oai:DiVA.org:uu-90197DiVA: diva2:162465
Available from: 2003-04-03 Created: 2003-04-03 Last updated: 2015-03-24Bibliographically approved
In thesis
1. Indirect Radiohalogenation of Targeting Proteins: Labelling Chemistry and Biological Characterisation
Open this publication in new window or tab >>Indirect Radiohalogenation of Targeting Proteins: Labelling Chemistry and Biological Characterisation
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In about half of all newly diagnosed cancer cases, conventional treatment is not adequately curative, mainly due to the failure of conventional techniques to find and kill residual cells and metastases, which might consist of only a few malignant cells, without causing unacceptable complications to healthy tissue. To solve the problem a more selective delivery of cytotoxic substances to tumour cells is needed. The approach applied here is called ‘tumour targeting’ and implies the use of biomolecules that recognise specific molecular structures on the malignant cell surface. Such molecules are then used for a selective transport of toxic agents to the cancer cells.

The use of radionuclides as cytotoxic substances has a number of advantages: 1) radiation does not cause severe resistance; 2) there is a cross-fire effect and 3) smaller amounts of nuclides are required than other cytotoxic substances to cause the same damage. Such an approach is called radionuclide tumour therapy. Several factors are important for the success of radionuclide therapy, such as the pharmacokinetics of the radiolabelled substance and its radiocatabolites, as well as the physical and chemical properties of the radiolabel used.

Nuclear properties of the label should be consistent with the problem to be solved: primary diagnostics; quantification of pharmacokinetics and dose planning; or therapy. From this point of view, radiohalogens are an attractive group of radiolabels. Halogens have nuclides with a variety of physical properties while the chemical and biological properties of halogens are very similar. The same labelling procedures can be used for all heavy halogens, i.e. bromine, iodine and astatine. It has been demonstrated that the biodistribution of proteins labelled with different heavy halogens is quite similar.

The main goal of the study was to develop protein radiohalogenation methods that provide a stable halogen-protein bond, convenient labelling chemistry that preserves the binding properties of proteins, long intracellular retention of radioactivity in targeted cells and quick release of radiohalogenated catabolites from the blood circulation. Radiohalogenation of proteins using indirect methods was studied, including optimisation of labelling chemistry and biological characterisation of some labelled conjugates. Two groups for indirect radiohalogenation were used, representing two different labelling principles: activated ester of benzoic acid (1) and the derivative of closo-dodecaborate anion (2). The non-phenolic linker (1) as well as the borate-halogen moiety (2) probably prevent dehalogenation. The negative charge of the potential catabolic products of (2) might trap radiohalogens intracellularly.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2003. 47 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1238
Cell and molecular biology, radiohalogenation, Cell- och molekylärbiologi
National Category
Biochemistry and Molecular Biology
Research subject
Biomedical Radiation Science
urn:nbn:se:uu:diva-3349 (URN)91-554-5576-X (ISBN)
Public defence
2003-04-26, Rudbeck Sal, Rudbeck Laboratoriet, Uppsala, 13:15
Available from: 2003-04-03 Created: 2003-04-03Bibliographically approved

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