Synthesis and characterization of an MRI Gd-based probe designed to target the translocator protein

Synthesis and characterization of an MRI Gd-based probe designed to target the translocator protein

Copyright © 2013 John Wiley & Sons, Ltd.

Bibliographische Detailangaben
Veröffentlicht in:Magnetic resonance in chemistry : MRC. - 1985. - 51(2013), 2 vom: 21. Feb., Seite 116-22
1. Verfasser: Cerutti, Erika (VerfasserIn)
Weitere Verfasser: Damont, Annelaure, Dollé, Frédéric, Baroni, Simona, Aime, Silvio
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2013
Zugriff auf das übergeordnete Werk:Magnetic resonance in chemistry : MRC
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Acetamides Biomarkers Molecular Probes N,N-diethyl-2-(2-(4-methoxyphenyl)-5,7-dimethyl-pyrazolo(1,5-a)pyrimidin-3-yl)-acetamide Pyrazoles Pyrimidines Receptors, GABA TSPO protein, human mehr... Gadolinium AU0V1LM3JT
Beschreibung
Zusammenfassung:Copyright © 2013 John Wiley & Sons, Ltd.
DPA-713 is the lead compound of a recently reported pyrazolo[1,5-a]pyrimidineacetamide series, targeting the translocator protein (TSPO 18 kDa), and as such, this structure, as well as closely related derivatives, have been already successfully used as positron emission tomography radioligands. On the basis of the pharmacological core of this ligands series, a new magnetic resonance imaging probe, coded DPA-C(6)-(Gd)DOTAMA was designed and successfully synthesized in six steps and 13% overall yield from DPA-713. The Gd-DOTA monoamide cage (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) represents the magnetic resonance imaging reporter, which is spaced from the phenylpyrazolo[1,5-a]pyrimidineacetamide moiety (DPA-713 motif) by a six carbon-atom chain. DPA-C(6)-(Gd)DOTAMA relaxometric characterization showed the typical behavior of a small-sized molecule (relaxivity value: 6.02 mM(-1) s(-1) at 20 MHz). The good hydrophilicity of the metal chelate makes DPA-C(6)-(Gd)DOTAMA soluble in water, affecting thus its biodistribution with respect to the parent lipophilic DPA-713 molecule. For this reason, it was deemed of interest to load the probe to a large carrier in order to increase its residence lifetime in blood. Whereas DPA-C(6)-(Gd)DOTAMA binds to serum albumin with a low affinity constant, it can be entrapped into liposomes (both in the membrane and in the inner aqueous cavity). The stability of the supramolecular adduct formed by the Gd-complex and liposomes was assessed by a competition test with albumin
Beschreibung:Date Completed 09.07.2013
Date Revised 19.11.2015
published: Print-Electronic
Citation Status MEDLINE
ISSN:1097-458X
DOI:10.1002/mrc.3919