10.1002/mrc.3919
https://zenodo.org/records/8521
oai:zenodo.org:8521
Cerutti, Erika
Erika
Cerutti
Dipartimento di Chimica and Centro di Imaging Molecolare, Università degli Studi di Torino, Via Nizza 52, 10126, Torino, Italy
Damont, Annelaure
Annelaure
Damont
CEA, I2BM, Service Hospitalier Frédéric Joliot, 4 Place du Général Leclerc, F-91406 Orsay, France
Dollé, Frédéric
Frédéric
Dollé
CEA, I2BM, Service Hospitalier Frédéric Joliot, 4 Place du Général Leclerc, F-91406 Orsay, France
Baroni, Simona
Simona
Baroni
Invento Srl, Via Nizza 52, Torino, Italy
Aime, Silvio
Silvio
Aime
Dipartimento di Chimica and Centro di Imaging Molecolare, Università degli Studi di Torino, Via Nizza 52, 10126, Torino, Italy
Synthesis and characterization of an MRI Gd-based probe designed to target the translocator protein.
Zenodo
2013
NMR
1H
MRI
contrast agents
relaxometry
Gd-complexes
DPA-713
TSPO
2013-01-10
https://zenodo.org/communities/inmind
https://zenodo.org/communities/eu
Creative Commons Attribution 4.0 International
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.
European Commission
10.13039/501100000780
278850
Imaging of Neuroinflammation in Neurodegenerative Diseases