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Site-specific antibody radiofluorination for positron emission tomography
KTH, School of Biotechnology (BIO).
2013 (English)Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesisAlternative title
Lägesspecifik radiofluorinering av antikroppar för positronemissionstomografi (Swedish)
Abstract [en]

The aim of this project was to label human antibodies for PET-applications with 18F via the IgG-binding Z-domain. The Z-domain was functionalized on its N-terminal in order to be able to attach a radioactive label by a cehmoselective reaction. For the labeling reaction, two strategies were used: oxime chemistry and click chemistry. The Z-domain could then be attached to the antibody by UV-conjugation, by inserting a benzoylphenylalanine (BPA) residue in the peptide ewquence. An aminoosy (AO)-functionalized Z-domain, AO-Z32BPA, was successfully synthesized and the aminooxy group was available for the oxime reaction, which is the method that will be used for labeling it. It was also shown that the aminooxy-functionalized Z-domain reained its ability to be covalently linke to an antibody by UV-conjugation. Z-domains were also prepared to take part in a click reaction., by coupling the dibenzocycllctyl (DBCO) group to the N-terminal of the peptide. No product was obtained from click reaction with an azido reagent, although several reaction conditions were tried. When introducing short-lived radiolabels to proteins for PET-imaging, time is crucial. An investigation of the UV-conjugation protocol was made, in order to decrease the time as much as possible. Results from the investigation of the UV-conjugation protocol show that the time of the protocol could be substantially reduced.

Place, publisher, year, edition, pages
Keyword [en]
Antibody labeling, PET, oxime chemistry, click chemistry, radiofluorination, UV conjugation, Z domain, benzoylphenylalanine
National Category
Engineering and Technology
URN: urn:nbn:se:kth:diva-150697OAI: diva2:744733
Available from: 2015-04-17 Created: 2014-09-08 Last updated: 2015-09-22Bibliographically approved

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