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Radiobromination of closo-carboranes using palladium-catalyzed halogen exchange
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry, Organic Chemistry II.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry, Organic Chemistry II.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry, Organic Chemistry II.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry, Organic Chemistry II.
2005 (English)In: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 48, no 3, 195-202 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2005. Vol. 48, no 3, 195-202 p.
Keyword [en]
halogen exchange, carboranes, [76Br]bromide, labelling, palladium, catalyst
National Category
Organic Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-69999DOI: 10.1002/jlcr.914OAI: oai:DiVA.org:uu-69999DiVA: diva2:97910
Available from: 2005-04-13 Created: 2005-04-13 Last updated: 2017-11-21Bibliographically approved
In thesis
1. Carborane Derivatives for Nuclide Therapy and Imaging: Synthesis and Radio-labelling
Open this publication in new window or tab >>Carborane Derivatives for Nuclide Therapy and Imaging: Synthesis and Radio-labelling
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis describes synthesis and radiohalogenation of closo-carborane and nido-carborate derivatives for application in nuclide therapy and imaging. The work could be divided in to four sections.

In the first section, the synthesis of three boronated DNA-intercalators – 1–(N-9-acridinyl-3-aminopropyl)-para-carborane-12-carboxylic acid hydrogen chloride, 1-[1-(N-9-acridinyl-3-aminopropyl)-para-carborane 12-(3-propyloxi)]-1,3-propanediol, 1-(N-9-acridinyl-3-amino-propyl)-1-ortho-carborane-2-ylmethoxy)1-3-propandiol – for potential use in BNCT, using targeted delivery is described.

The second section describes the application of the Heck-reaction to 2-iodo-para-carborane, which has successfully been reacted with a number of styrene derivatives, i.e. para-phenyl, chloro, bromo, nitro, methoxy, and methyl-styrene, to furnish the desired trans-β-2-B-para-carborane)styrene.

In the third section, radio-iodination and radio-bromination of closo-carboranes is described. Reaction of the corresponding iodinated carborane, in the presence of palladium catalyst, [125I]iodinated and [76Br]brominated carboranes were obtained in high to excellent yields.

Section four describes a method for indirect radiolabelling of antibodies with 76Br. It was shown that NBI, a isothiocyanatobenzene derivative of dodecahydro-7,8-dicarba-nido-undecaborate anion, could be radio-brominated using oxidative conditions. The radio-brominated NBI was thereafter conjugated to anti-HER2 antibody for biological evaluation.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2003. 52 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1104-232X ; 881
Keyword
Organic chemistry, Organisk kemi
National Category
Organic Chemistry
Research subject
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-3561 (URN)91-554-5722-3 (ISBN)
Public defence
2003-10-02, B22, BMC, Uppsala, 10:15 (English)
Opponent
Supervisors
Available from: 2003-09-09 Created: 2003-09-09 Last updated: 2009-11-23Bibliographically approved
2. Radiohalogenated Compounds for Tumor Targeting: Synthesis and Radiolabeling
Open this publication in new window or tab >>Radiohalogenated Compounds for Tumor Targeting: Synthesis and Radiolabeling
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis describes the synthesis and radiohalogenation of compounds of potential use for tumor targeting.

The first section describes the synthesis and radioiodination of DNA intercalating compounds. The compounds are derivatives of 9-aminoacridine, and the anthracyclins daunorubicin and doxorubicin. The precursor compounds were labeled with 125I (T1/2 = 60 days), which is an Auger emitting nuclide. 125I decaying in the close vicinity of DNA is known to have a much higher cell killing effect than 125I decaying in the cytoplasm and some of the labeled compounds prepared in this thesis are currently being tested for use in targeted radionuclide therapy for cancer.

The second section describes the radiobromination of closo-carboranes by subjecting the corresponding iodinated compounds to palladium-catalyzed halogen exchange using [76Br]bromide. The 76Br isotope (T1/2 = 16.2 h) is a positron emitting nuclide that is suitable for PET studies. Via the halogen exchange reaction good to excellent radiochemical yields of radiobrominated closo-carboranes were obtained. The results of the present study may prove to be applicable to pharmacokinetic studies of carboranes and their derivatives.

The third and final section describes the indirect radiobromination of the trastuzumab anti-HER2 monoclonal antibody and of the anti-HER2 Affibody by means of an “one-pot” procedure using N-succinimidyl-5-(tributylstannyl)-3-pyridinecarboxylate (SPC) and ((4-hydroxyphenyl)ethyl))maleimide (HPEM), respectively. It was found that SPC and HPEM can be efficiently radiobrominated and thereafter coupled to the antibody and Affibody, respectively. The labeled proteins retained their capacity to bind specifically to HER2 expressing SKOV-3 cells in vitro. Application of this method to 76Br might enable the use of PET in the detection of HER2 expression in breast, ovarian, and urinary bladder carcinomas.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2005. 51 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 22
Keyword
Inorganic chemistry, 9-Aminoacridine, Daunorubicin, Doxorubicin, Carborane, Radiobromination, Radioiodination, Affibody, Monoclonal antibody, Oorganisk kemi
National Category
Inorganic Chemistry
Identifiers
urn:nbn:se:uu:diva-4817 (URN)91-554-6165-4 (ISBN)
Public defence
2005-04-25, Room B42, BMC, Husargatan 3, Uppsala, 10:15 (English)
Opponent
Supervisors
Available from: 2005-03-04 Created: 2005-03-04 Last updated: 2009-11-23Bibliographically approved

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Mume, EskenderTolmachev, VladimirSjöberg, Stefan

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