Gadolinium DO3A derivatives mimicking phospholipids; preparation and in vitro evaluation as pH responsive MRI contrast agents

Hovland, Ragnar; Gløgård, Christian; Aasen, Arne J.; Klaveness, Jo

doi:10.1039/b100405k

Cited by 60 publications

(38 citation statements)

References 9 publications

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“…At high pH the deprotonated amine chelates prevent water access and the MR signal is low. Hovland et al (101) have prepared a DO3A compound with a tertiary amine-containing two long alkyl chains. When the amine is protonated (pH ¼ 3-6) the relaxivity is low.…”

Section: Ph-sensitive Agentsmentioning

confidence: 99%

Classification and basic properties of contrast agents for magnetic resonance imaging

Geraldes

Laurent

2009

Contrast Media & Molecular

485

409

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A comprehensive classification of contrast agents currently used or under development for magnetic resonance imaging (MRI) is presented. Agents based on small chelates, macromolecular systems, iron oxides and other nanosystems, as well as responsive, chemical exchange saturation transfer (CEST) and hyperpolarization agents are covered in order to discuss the various possibilities of using MRI as a molecular imaging technique. The classification includes composition, magnetic properties, biodistribution and imaging applications. Chemical compositions of various classes of MRI contrast agents are tabulated, and their magnetic status including diamagnetic, paramagnetic and superparamagnetic are outlined. Classification according to biodistribution covers all types of MRI contrast agents including, among others, extracellular, blood pool, polymeric, particulate, responsive, oral, and organ specific (hepatobiliary, RES, lymph nodes, bone marrow and brain). Various targeting strategies of molecular, macromolecular and particulate carriers are also illustrated.

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Section: Ph-sensitive Agentsmentioning

confidence: 99%

Classification and basic properties of contrast agents for magnetic resonance imaging

Geraldes

Laurent

2009

Contrast Media & Molecular

485

409

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“…Among them there are metal complexes such as [Gd(BOPTA)(H 2 O)] 2- [3], [Gd(EOB-DTPA) (H 2 O)] 2- [4,5] and [Mn(DPDP)(H 2 O)] [6,7,8] (the last one cannot be applied at high doses owing to dissociation of the complex [9]), or superparamagnetic iron oxides, which are taken up by the reticuloendothelial system because of rapid phagocytosis [10]. Recently, liposomal and micellar paramagnetic contrast agents have also been proposed for this purpose [11,12,13,14,15]. Micelles are known to mimic the phospholipid structure of the membranes and hence can be good candidates as hepatocyte-specific agents.…”

Section: Introductionmentioning

confidence: 99%

From monomers to micelles: investigation of the parameters influencing proton relaxivity

et al. 2002

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17O NMR and (1)H NMRD studies have been performed on a series of Gd(III) 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) derivatives as potential liver-specific magnetic resonance imaging (MRI) contrast agents. They bear aliphatic side chains which make them capable of micellar self-organization. The compounds differ in the length (C10-C18) and in the chemical nature (alkyl or monoamide-alkyl) of their lipophilic chain. We have established a convenient method to determine the critical micellar concentration (cmc) of paramagnetic surfactants by (1)H relaxivity measurements. This technique can be easily used over a large temperature range; thus, it can find wide application outside the field of MRI contrast agents. The knowledge of the cmc allowed us to determine the parameters governing the water proton relaxivity of the Gd(III) chelates in both nonaggregated and aggregated micellar forms. The relaxation data of the micellar complexes have been interpreted with the Lipari-Szabo approach. This model allows a local motion to be separated from the global tumbling of the whole micelle (modulated by a local, tau(l), and a global, tau(g), rotational correlation time, respectively). The aggregation substantially affects the rotational dynamics and thus increases the proton relaxivity of the Gd(III) chelates. The global rotational correlation times increase with increasing length of the side chain (500-2800 ps for C10-C18). Local motions are also influenced by the length and by the hydrophobicity of the side chain. The analysis of the relaxation data reveals considerable flexibility for these micellar aggregates. The rate of water exchange obtained for these chelates is identical to that for [Gd(DOTA)(H(2)O)](-) (k(ex)(298)= 4.8 x 10(6)s(-1))and is not sensitive either to micellization or to differences in the aliphatic chain. A relaxivity gain in such systems could be attained by simultaneously optimizing the water exchange by modifications of the chelate and increasing the micelle rigidity by using water-soluble surfactants with more hydrophobic side chains.

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“…The introduction of the pendant arm can be performed by monosubstitution of cyclen as well as by reaction with its acetic acid derivatives in the free or esterified forms. The reaction can be performed under various conditions: So, aqueous or alcohol solutions are used for hydrophilic derivatives [294][295][296]. Alcohols, MeCN, or DMF are the most common solvents for reaction of hydrophobic oxiranes or for reaction of esterified macrocycle derivatives [105,[297][298][299].…”

Section: Derivatives Containing Alcoholic/phenolic Pendant Armmentioning

confidence: 99%

Synthesis and Characterization of Ligands and their Gadolinium(III) Complexes

Kotek¹,

Kubíček²,

Hermann³

et al. 2013

The Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging

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Gadolinium DO3A derivatives mimicking phospholipids; preparation and in vitro evaluation as pH responsive MRI contrast agents

Cited by 60 publications

References 9 publications

Classification and basic properties of contrast agents for magnetic resonance imaging

Classification and basic properties of contrast agents for magnetic resonance imaging

From monomers to micelles: investigation of the parameters influencing proton relaxivity

Synthesis and Characterization of Ligands and their Gadolinium(III) Complexes

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