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• Iovkova-Berends, L
• Wängler, C
• Zöller, T
• Höfner, G
• Wanner, K
• Rensch, C
• Bartenstein, P
• Kostikov, A
• Schirrmacher, R
• Jurkschat, K
• Wängler, B
• [+] on Google Scholar
• Iovkova-Berends, L
• Wängler, C
• Zöller, T
• Höfner, G
• Wanner, K
• Rensch, C
• Bartenstein, P
• Kostikov, A
• Schirrmacher, R
• Jurkschat, K
• Wängler, B
• [+] on PubMed
• Iovkova-Berends, L
• Wängler, C
• Zöller, T
• Höfner, G
• Wanner, K
• Rensch, C
• Bartenstein, P
• Kostikov, A
• Schirrmacher, R
• Jurkschat, K
• Wängler, B

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Molecules 2011, 16(9), 7458-7479; doi:10.3390/molecules16097458

Article

t-Bu₂SiF-Derivatized D₂-Receptor Ligands: The First SiFA-Containing Small Molecule Radiotracers for Target-Specific PET-Imaging

Ljuba Iovkova-Berends ¹ , Carmen Wängler ² , Thomas Zöller ¹ , Georg Höfner ³ , Klaus Theodor Wanner ³ , Christian Rensch ⁴ , Peter Bartenstein ² , Alexey Kostikov ⁵ , Ralf Schirrmacher ⁵ , Klaus Jurkschat ^1,*  and Björn Wängler ^2,*

¹ Department of Inorganic Chemistry II, Faculty of Chemistry, TU Dortmund, Otto-Hahn-Str. 6, 44221 Dortmund, Germany ² Department of Nuclear Medicine, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany ³ Department of Pharmacy, Center for Drug Research, Ludwig-Maximilians-University, Butenandtstr. 7, 81377 Munich, Germany ⁴ GE Global Research, 85748 Garching, Germany ⁵ McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, 3801 University St., Montreal H3A 2B4, QC, Canada

* Authors to whom correspondence should be addressed.

Received: 28 July 2011; in revised form: 19 August 2011 / Accepted: 31 August 2011 / Published: 2 September 2011

(This article belongs to the Special Issue Fluorine Chemistry)

Download PDF Full-Text [616 KB, uploaded 2 September 2011 11:27 CEST]

Abstract: The synthesis, radiolabeling and in vitro evaluation of new silicon-fluoride acceptor (SiFA) derivatized D₂-receptor ligands is reported. The SiFA-technology simplifies the introduction of fluorine-18 into target specific biomolecules for Positron-Emission-Tomography (PET). However, one of the remaining challenges, especially for small molecules such as receptor-ligands, is the bulkiness of the SiFA-moiety. We therefore synthesized four Fallypride SiFA-conjugates derivatized either directly at the benzoic acid ring system (SiFA-DMFP, SiFA-FP, SiFA-DDMFP) or at the butyl-side chain (SiFA-M-FP) and tested their receptor affinities. We found D₂-receptor affinities for all compounds in the nanomolar range (K_i(SiFA-DMFP) = 13.6 nM, K_i(SiFA-FP) = 33.0 nM, K_{i(SiFA-DDMFP)} = 62.7 nM and K_i(SiFA-M-FP) = 4.21 nM). The radiofluorination showed highest yields when 10 nmol of the precursors were reacted with [¹⁸F]fluoride/TBAHCO₃ in acetonitrile. After a reversed phased cartridge purification the desired products could be isolated as an injectable solution after only 10 min synthesis time with radiochemical yields (RCY) of more than 40% in the case of SiFA-DMFP resulting in specific activities >41 GBq/µmol (>1,100 Ci/mmol). Furthermore, the radiolabeled products were shown to be stable in the injectable solutions, as well as in human plasma, for at least 90 min.

Keywords: fluorine; isotopic labeling; positron emission tomography; radiopharmaceuticals; silicon

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