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[F-18]/F-19 exchange in fluorine containing compounds for potential use in F-18-labelling strategies
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry. (Bengt Långström)
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
2009 (English)In: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 52, no 12, 504-511 p.Article in journal (Refereed) Published
Abstract [en]

Exchange of [F-18]fluoride with F-19 in various organofluorine compounds in concentrations ranging from 0.06 to 56 mM was explored. We aimed to explore whether exchange reactions can be a potential useful labelling strategy, when there are no requirement of high specific radioactivity. Parameters such as solvents, temperature, conventional vs microwave heating, and the degree of fluorine load in some aromatic and alkyl compounds were investigated with regard to radiochemical yield and specific radioactivity. A series of fluorobenzophenones (1-6), 1-(4-fluorophenyl)ethanone (7), various activated and deactivated fluoro benzenes (8-16), N-(pentafluorophenyl)benzamide (17), (pentafluorophenyl)formamide (18), (tridecafluorohexyl) benzene (19) and tetradecafluorohexane (20) were subjected to [F-18]/F-19 exchange. To test this strategy to label biologically active molecules containing fluorine atoms in an aryl group, two analogues of WAY-100635 (21-22), Lapatinib (23), 2,5,6,7,8-pentafluoro-3-methyinaphthoquinone (24) and 1-(2,4-difluorophenyl)-3-(4-fluorophenyl)propan-l-one (25) were investigated. The multi-fluorinated molecules containing an electron-withdrawing group were successfully labelled at room temperature, whereas the monofluorinated, as well as those containing an electron-donating group, required heating for the exchange reaction to take place.

Place, publisher, year, edition, pages
2009. Vol. 52, no 12, 504-511 p.
Keyword [en]
nucleophilic 18F-fluorination, halogen exchange, organofluorine compounds, perfluoro compounds
National Category
Other Basic Medicine
URN: urn:nbn:se:uu:diva-107278DOI: 10.1002/jlcr.1670ISI: 000272471500011OAI: oai:DiVA.org:uu-107278DiVA: diva2:249028
Available from: 2009-10-09 Created: 2009-08-03 Last updated: 2011-03-03Bibliographically approved
In thesis
1. Development of 18F- and 68Ga-Labelled Tracers: Design Perspectives and the Search for Faster Synthesis
Open this publication in new window or tab >>Development of 18F- and 68Ga-Labelled Tracers: Design Perspectives and the Search for Faster Synthesis
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis deals with the design of 18F- and 68Ga-labelled positron emission tomography (PET) tracers and the development of technologies that enable faster and simpler preparation with high specific radioactivity. Techniques like microwave heating and reducing the concentrations of the precursor were investigated with this perspective. A few applications were explored using molecular design perspectives.

A nucleophilic 18F-labelling strategy using perfluoro-containing leaving groups was explored. We observed that [18F]fluoride was interacting with the perfluoro alkyl chains of the substrate, preventing the nucleophilic substitution from taking place. When a perfluoroaryl group was instead used in the leaving group, the substitution took place and purification by fluorous solid-phase extraction was possible.

18F-Labelled analogues of the monoamine oxidase-A inhibitor harmine were prepared by one-step nucleophilic fluorinations and evaluated by in vitro autoradiography, showing high specific binding.

Biotin analogues labelled with 18F and 68Ga were prepared and their binding to avidin evaluated. All analogues retained their binding ability and will be further evaluated in transplantation models with avidin-coated islets of Langerhans.

Peptide design perspectives were used in some examples where the Arg-Gly-Asp (RGD) sequence and a single-chain version of vascular endothelial growth factor (VEGF) protein functionalized with 2,2',2'',2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid (DOTA) or 2,2',2''-(1,4,7-triazonane-1,4,7-triyl)triacetic acid (NOTA) as chelators were labelled with 68Ga. The RGD motif and VEGF have high affinity for, respectively, αvβ3 integrin and VEGFR-2 receptor that are overexpressed in angiogenesis process. The 68Ga-labelled scVEGF maintained its functional activity in vitro.

A polypeptide conjugate containing phosphocholine, which has affinity for the C-reactive protein released during the inflammatory process, was labelled with 68Ga for the development of an imaging agent for inflammation in vivo.

Finally [18F]/19F exchange in fluorine-containing compounds was studied in order to investigate whether the exchange reaction can be of practical use for labelling.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 48 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 678
PET, nucleophilic 18F-fluorination, perfluoro, F-SPE, molecular design, 68Ga, chelators, DOTA, NOTA, microwave, halogen exchange, harmine, biotin, RGD, VEGF, CRP
National Category
Chemical Sciences
Research subject
Organic Chemistry
urn:nbn:se:uu:diva-108629 (URN)978-91-554-7626-7 (ISBN)
Public defence
2009-11-26, C8:305, BMC, Husargatan 3, 751 23 Uppsala, Uppsala, 13:15 (English)
Available from: 2009-11-05 Created: 2009-09-24 Last updated: 2011-03-03Bibliographically approved

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Blom, ElisabethKarimi, FarhadLångström, Bengt
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