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Synthesis, Characterization, and Biodistribution of a Dinuclear Gadolinium Complex with Improved Properties as a Blood Pool MRI Agent
Author(s) -
La Cava Francesca,
Fringuello Mingo Alberto,
Miragoli Luigi,
Terreno Enzo,
Cappelletti Enrico,
Lattuada Luciano,
Poggi Luisa,
Colombo Serra Sonia
Publication year - 2018
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201800052
Subject(s) - biodistribution , gadolinium , chemistry , chelation , dota , mri contrast agent , deoxycholic acid , conjugated system , nuclear chemistry , nuclear magnetic resonance , in vitro , organic chemistry , biochemistry , bile acid , physics , polymer
A dinuclear gadolinium(III) chelate containing two moieties of diethylenetriaminepentaacetic acid (DTPA), covalently conjugated to an analogue of deoxycholic acid, was synthesized and thoroughly characterized. A full relaxometric analysis was carried out, consisting of 1) the acquisition of nuclear magnetic resonance dispersion (NMRD) profiles in various media; 2) the study of binding affinity to serum albumin; 3) the measurement of 17 O transverse relaxation rate versus temperature, and 4) a transmetallation assay. In vivo biodistribution MRI studies at 1 T and blood pharmacokinetics assays were carried out in comparison with Gd‐DTPA (Magnevist) and gadocoletic acid trisodium salt (B22956/1), two well‐known Gd complexes that share the same chelating cage and the same deoxycholic acid residue of the Gd complex investigated herein ((GdDTPA) 2 ‐Chol). High affinity for plasma protein and, in particular, the availability of more than one binding site, allows the complex to reach a fairly high relaxivity value in plasma (∼20 m m −1 s −1 , 20 MHz, 310 K) as well as to show unexpectedly enhanced properties of blood pooling, with an elimination half‐life in rats approximately seven times longer than that of B22956/1.