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Radiohalogenation of biomolecules: An experimental study on radiohalogen preparation, precursor synthesis, radiolabeling and biodistribution
Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry.
1998 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Radiohalogens are widely used in nuclear medicine, both as tool for diagnostic in vivo imaging and inradionuclide therapy. This study deals with the use of radiohalogens; separation, precursor synthesis, labeling and biological behavior. The focus is on 211At and 124I, the former being a candidate for nuclide therapy and the latter potentially useful for diagnostic imaging and Auger-electron based radiotherapy. For astatine the separation, labeling and some biological behavior is described, and for iodine the latter two.

Astatine was separated from an irradiated bismuth target by dry distillation. A novel cryotrap wasdeveloped for the isolation of astatine and subsequent synthesis of radiolabeled compounds. 5-[211At]astato-2´-deoxyuridine (AUdR) and N-succinimidyl-4-[211At]astatobenzoate (SAB) were synthesized in ~95% respectively ~90% radiochemical yields. The former is incorporated into DNA of proliferating cells and can therefore be used as an endoradiotherapeutic agent. The latter is a conjugate for the astatination of proteins. Human epidermal growth factor (hEGF) was tagged with astatine using three approaches: a) direct labeling of native hEGF, b) conjugation with SAB, and c) direct labeling of an hEGF - 7-(3-aminopropyl)-7,8-dicarba-nido-undecaborate(l-) conjugate. The overall labeling yields were ~3.5% for direct labeling, ~44% for SAB and ~70% for the hEGF-nido-carborane conjugate.

A new route to N-succinimidyl 3- and 4- [124I]iodobenzoate, two reagents for radioiodination of proteins is described affording 90% radiochemical yield. Three radioiodinated analogs of PK11195, 1-(2-chlorophenyl)-N-methyl-N-(l-methylpropyl)isoquinoline-3-carboxyamide, a peripheral-type benrodiazepine receptor antagonist, were synthesized. All three analogs were obtained in >90% radiochemical yield. Synthesis and application of 5-[124I]iodo-2´-deoxyuridine (IUdR) is presented.

The close-dodecaborate anion was evaluated as prosthetic group for radioiodination of macromolecules. Its inertness to in vivo dehalogenation was demonstrated by low thyroidal radioiodine uptake in the rat (0.07% ID/g, 20 h post injection).

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 1998. , 57 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1104-232X ; 380
Keyword [en]
Keyword [sv]
National Category
Chemical Sciences
Research subject
Organic Chemistry
URN: urn:nbn:se:uu:diva-902ISBN: 91-554-4264-1OAI: oai:DiVA.org:uu-902DiVA: diva2:172292
Public defence
1998-10-23, the Svedberg Lecture Hall, Institute of Chemistry, Uppsala University, Uppsala, 10:15
Available from: 1998-10-02 Created: 1998-10-02Bibliographically approved

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