Improved syntheses of P2X7 ligands based on substituted benzyl amide of pyroglutamic acid motif labelled with iodine-123 or iodine-125

Author:

Marešová Anna,Jurášek MichalORCID,Zimmermann Tomáš,Drašar Pavel,Petřík Miloš,Džubák Petr,Lindegren Sture,Cumming Paul,Pichler Robert,Popkov Alexander

Abstract

Abstract P2X7 sites are emerging targets for molecular imaging research, notably in the context of neurodegeneration and inflammatory conditions. Therefore, we prepared a precursor for (radio)iodination of the P2X7 ligand VPGIS191. We then developed a radioiodination method with 123I for SPECT with a radiochemical yield of 71 ± 13% and 125I for autoradiography with a radiochemical yield of 85 ± 6% Autoradiography of [125I]VPGIS191 in mouse brain cryostat sections demonstrated approximately 36 nM binding affinity and Bmax of approximately 400 pmol/gram tissue for P2X7 binding sites. VPGIS191 (cis) had a two-fold lower affinity compared to its geometric trans-isomer TZ6019. Graphical abstract

Funder

Ministerstvo Školství, Mládeže a Tělovýchovy

EU - Next Generation EU

University of Chemistry and Technology, Prague

Publisher

Springer Science and Business Media LLC

Subject

Health, Toxicology and Mutagenesis,Public Health, Environmental and Occupational Health,Spectroscopy,Pollution,Radiology, Nuclear Medicine and imaging,Nuclear Energy and Engineering,Analytical Chemistry

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