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Author:
Winberg, Karl Johan (Uppsala University, Department of Chemistry)
Title:
Carborane Derivatives for Nuclide Therapy and Imaging: Synthesis and Radio-labelling
Department:
Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry
Publication type:
Doctoral thesis, comprehensive summary (Other academic)
Language:
English
Place of publ.:
Uppsala
Publisher:
Acta Universitatis Upsaliensis
Pages:
52
Series:
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1104-232X; 881
Year of publ.:
2003
URI:
urn:nbn:se:uu:diva-3561
Permanent link:
http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3561
ISBN:
91-554-5722-3
Subject category:
Organic chemistry
Research subject:
Organic Chemistry
Keywords(en) :
Organic chemistry
Keywords(sv) :
Organisk kemi
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.

Public defence:
2003-10-02, B22, BMC, Uppsala, 10:15
Degree:
degree of Doctor of Philosophy
Supervisor:
Sjöberg, Stefan, Professor
Opponent:
Szabó, Kálmán, Professor (Kemiska, Stockholm)
Available from:
2003-09-09
Created:
2006-03-19
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