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Article Dans Une Revue Contrast Media and Molecular Imaging Année : 2008

In vivo MRI assessment of a novel GdIII-based contrast agent designed for high magnetic field applications

Résumé

Gd 3 L is a trinuclear Gd 3R complex of intermediate size, designed for contrast agent applications in high field magnetic resonance imaging (H 12 L is based on a trimethylbenzene core bearing three methylene-diethylenetriamine-N,N,N 00 ,N 00-tetraacetate moieties). Thanks to its appropriate size, the presence of two inner sphere water molecules and a fast water exchange, Gd 3 L has remarkable proton relaxivities at high magnetic field (r 1 ¼ 10.2 vs 3.0 mM S1 s S1 for GdDOTA at 9.4 T, 37-C, in H 2 O). Here we report an in vivo MRI feasibility study, complemented with dynamic g scintigraphic imaging and biodistribution experiments using the 153 Sm-enriched analog. MRI experiments were performed at 9.4 T in mice with Gd 3 L and the commercial contrast agent gadolinium(III)-1,4,7,10tetraazacyclododecane-1,4,7,10-tetraacetate (GdDOTA). Gd 3 L was well tolerated by the animals at the dose of 8 mmol Gd kg S1 body weight. Dynamic contrast enhanced (DCE) images showed considerably higher signal enhancement in the kidney medulla and cortex after Gd 3 L injection than after GdDOTA injection at an identical dose. The relaxation rates, DR 1 , were calculated from the IR TrueFISP data. During the excretory phase, the DR 1 for various tissues was similar for Gd 3 L and GdDOTA, when the latter was injected at a threefold higher dose (24 vs 8 mmol Gd kg S1 body weight). These results point to an approximately three times higher in vivo relaxivity (per Gd) for Gd3L relative to GdDOTA, thus the ratio of the relaxivities of the two compounds determinedin vitrois retainedunderin vivoconditions. They also indicate that the two inner sphere water molecules per Gd in Gd3L are notsubstantially replaced by endogenous anions or other donor groups under physiological conditions. Gd3L has apharmacokinetics typical of small, hydrophilic complexes, involving fast renal clearance and no retention in the bloodpool. The dynamicgscintigraphic studies and the biodistribution experiments performed in Wistar rats with153Sm-enriched*Sm3L are also indicative of a fast elimination via the kidneys.
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Dates et versions

hal-03059411 , version 1 (12-12-2020)

Identifiants

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Paulo Loureiro de Sousa, João Bruno Livramento, Lothar Helm, André E Merbach, William Même, et al.. In vivo MRI assessment of a novel GdIII-based contrast agent designed for high magnetic field applications. Contrast Media and Molecular Imaging, 2008, 3 (2), pp.78 - 85. ⟨10.1002/cmmi.233⟩. ⟨hal-03059411⟩
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