uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Synthesis and in vitro evaluation of 18F-labelled di- and tri(ethylene glycol) metomidate esters
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry. (Bengt Långström)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
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 7-8, 278-285 p.Article in journal (Refereed) Published
Abstract [en]

By replacing the alkyl chain in a metomidate ester with F-18-labelled   di- or tri(ethylene glycol) chains, two F-18-labelled PET tracers, i.e.  2-(2-[F-18]fluoroethoxy)ethyl 1-[(1R)-1-phenylethyll-1   H-imidazole-5-carboxylate (1) and   2-[2-(2-[F-18]fluoroethoxy)-ethoxylethyl   1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (2), were   synthesized. Two precursors, 2-(2-bromoethoxy)ethyl  1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate and   2-[2-(2-chloroethoxy)ethoxylethyl  1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate, were prepared and   used in one-step nucleophilic [F-18]fluorination reactions using   conventional and microwave heating. Organ distribution, frozen section   autoradiography and metabolite analysis were performed. The   decay-corrected radiochemical yields of 1 and 2 were 26 +/- 8 and 23   +/- 8%, respectively, when they were prepared using conventional   heating. By performing microwave heating, the reaction time could be   decreased and the yields of analogues 1 and 2 could be increased to 57   +/- 12 and 51 +/- 18%, respectively. Organ distribution studies in the   rat showed considerable uptake in the lungs, adrenals and liver. Both   compounds bound with low nonspecific binding (1: approx. 20-30%; 2:   2.9% or lower) to tissue from pig and human normal and pathologic   adrenals. Metabolite analyses were performed in rats after 5 and 30 min   for tracer 1 (20 +/- 6 and 2 +/- 1 %) and tracer 2 (27 +/- 5 and 6 +/-   4%). Both compounds are interesting candidates for the detection of   different types of adrenal disorders.

 

Place, publisher, year, edition, pages
2009. Vol. 52, no 7-8, 278-285 p.
Keyword [en]
n.c.a. nucleophilic 18F-fluorination, di- and tri(ethylene glycol), metomidate, analogues
National Category
Chemical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-88794DOI: 10.1002/jlcr.1597ISI: 000268690300029OAI: oai:DiVA.org:uu-88794DiVA: diva2:159147
Available from: 2009-02-06 Created: 2009-02-06 Last updated: 2012-08-03Bibliographically approved
In thesis
1. Imaging of Enzymes in the Steroid Biosynthetic Pathway: Synthesis of 18F-Labelled Tracers
Open this publication in new window or tab >>Imaging of Enzymes in the Steroid Biosynthetic Pathway: Synthesis of 18F-Labelled Tracers
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis deals with the synthesis and development of 18F-labelled alkyl etomidate and vorozole analogues, and their use as positron emission tomography (PET) tracers for the imaging of the steroid enzymes 11β-hydroxylase and aromatase. Two synthetic 18F-labelling approaches to the etomidate and vorozole analogues were developed, and the analogues were evaluated in some biological assays.

The two-step labelling method was used to synthesise many compounds for biological evaluation. In the first step, a 18F-labelled intermediate based on a ditosylate or a halogenated diethyl ether was synthesised and used directly in the next alkylation step. The decay-corrected (d.c.) radiochemical yield was higher compared to other known two-step labelling methods.

Once an appropriate candidate has been chosen for clinical evaluation, a one-step labelling method will be more suitable. We therefore developed a method based on precursors that had leaving groups at the end of their alkyl chains, and used these directly in the 18F-labelling synthesis. The one-step 18F-labelling synthesis required less reaction time and produced higher specific radioactivity and d.c. radiochemical yield than our two-step synthesis. With microwave heating, the reaction time was reduced to seconds and the d.c. radiochemical yield was better than that obtained with conventional heating. The one-step synthesis simplified the technical handling by allowing the tracer syntheses to be automated on the TRACERLab FXFN.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 54 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 607
National Category
Organic Chemistry
Research subject
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-89177 (URN)978-91-554-7424-9 (ISBN)
Public defence
2009-03-21, B42, BMC, Husargatan 3, Uppsala, 10:15 (English)
Opponent
Supervisors
Available from: 2009-02-26 Created: 2009-02-06 Last updated: 2013-05-30Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Authority records BETA

Erlandsson, Maria

Search in DiVA

By author/editor
Erlandsson, Maria
By organisation
Department of Biochemistry and Organic ChemistryDepartment of Public Health and Caring Sciences
In the same journal
Journal of labelled compounds & radiopharmaceuticals
Chemical Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 518 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf