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

Authors :
Björn Wängler
Klaus Jurkschat
Ralf Schirrmacher
Alexey Kostikov
Christian Rensch
Peter Bartenstein
Klaus Theodor Wanner
Georg Höfner
Thomas Zöller
Carmen Wängler
Ljuba Iovkova-Berends
Source :
Molecules, Vol 16, Iss 9, Pp 7458-7479 (2011)
Publication Year :
2011
Publisher :
MDPI AG, 2011.

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 (Ki(SiFA-DMFP) = 13.6 nM, Ki(SiFA-FP) = 33.0 nM, Ki(SiFA-DDMFP) = 62.7 nM and Ki(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.

Details

Language :
English
ISSN :
14203049
Volume :
16
Issue :
9
Database :
Directory of Open Access Journals
Journal :
Molecules
Publication Type :
Academic Journal
Accession number :
edsdoj.8c491236d6294266aa96f7cecf7234c4
Document Type :
article
Full Text :
https://doi.org/10.3390/molecules16097458