Synthesis of a new gadolinium complex with a high affinity for human serum albumin and its manifold physicochemical characterization by proton relaxation rate analysis, NMR diffusometry and electrospray mass spectrometry

Henoumont, Céline; Henrotte, Virginie; Laurent, Sophie; Elst, Luce Vander; Müller, Robert N.

doi:10.1016/j.jinorgbio.2007.10.017

Cited by 27 publications

(18 citation statements)

References 52 publications

(85 reference statements)

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“…To satisfy the dual challenge of high target affinity and high relaxivity, protein-bound chelates offer unique possibilities which have been the most exploited in developing blood pool agents via serum albumin binding. Other Gd(III) complexes bearing different moieties capable of protein binding have been reported such as MP-2269 (Chart 2.4) [199][200][201][202][203]. Serum albumin binding confines the contrast agent to the blood vessels and avoids rapid kidney wash-off, which allows for imaging of different vascular regions with a single injection (magnetic resonance angiography).…”

Section: Non-covalent Binding: Protein-bound Chelatesmentioning

confidence: 99%

Relaxivity of Gadolinium(III) Complexes: Theory and Mechanism

Tóth

Helm

Merbach

2013

The Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging

105

131

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The aim of using a contrast agent in Magnetic Resonance Imaging is to accelerate the relaxation of water protons in the surrounding tissue. This objective can be achieved by paramagnetic substances. In 1948, Bloch et al. reported the use of the paramagnetic ferric nitrate salt to enhance the relaxation rates of water protons [1]. Some 30 years later, Lauterbur et al. applied a Mn(II) salt to distinguish between different tissues based on the differential relaxation times and thus produced the first MR image [2]. Nowadays, Gd(III) complexes are far the most widely used MRI contrast agents in the clinical practice. The choice of Gd(III) is explained by its seven unpaired electrons which makes it the most paramagnetic stable metal ion. Beside this, Gd(III) has another significant feature: owing to the symmetric S-state, its electronic relaxation is relatively slow which is relevant to its efficiency as an MRI contrast agent.As most of the current contrast agent applications in MRI concerns Gd(III) complexes, this chapter will focus on the discussion of relaxation theory and the experimental results on Gd(III)-based agents. Several reviews have been published on this topic [3][4][5][6][7]. In addition to Gd(III) compounds, a Mn(II) chelate, Mn(II)DPDP, is the only metal complex which has been approved as an MRI contrast agent (DPDP = N,N -dipyridoxylethylenediamine-N,N -diacetate 5,5 -bis(phosphate)) [8]. Mn(II)DPDP is a weak chelate that dissociates in vivo to give free manganese which is taken up by hepatocytes [9]. The presence of the ligand is necessary because it facilitates a slower release of manganese than would have been the case had manganese been administered as a simple salt, such as manganese chloride.

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Section: Non-covalent Binding: Protein-bound Chelatesmentioning

confidence: 99%

Relaxivity of Gadolinium(III) Complexes: Theory and Mechanism

Tóth

Helm

Merbach

2013

The Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging

105

131

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“…We tested the efficacy of Chelex® 100, which is a styrene-divinylbenzene co-polymer containing iminodiacetic acid groups and is well known for its ability to bind metal ions (25)(26)(27). It has, for example, been successfully applied in removing the free gadolinium, lanthanum, and europium ions from their complex solutions (28). We produced 71 Ga NMR spectra of a Ga-DOTA solution before and after treatment with 5% Chelex ® 100 (Fig.…”

Section: Resultsmentioning

confidence: 99%

NMR determination of free gallium(III) ions in aqueous solutions of Ga complexes, “cold” analogs of PET/SPECT tracers

Zhou

Henoumont

Elst

et al. 2011

Contrast Media & Molecular

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Ga complexes are widely used as radiopharmaceuticals for PET or SPECT imaging and as therapeutic agents. At physiological pH, free gallium(III) ions can stably exist as soluble gallate [Ga(OH)4]−, a nephrotoxic compound whose presence should be avoided. Any Ga complex, therefore, should be carefully checked for the absence of gallate before use. Here we show that 71Ga NMR is a useful tool to rapidly detect the presence of gallate in aqueous solutions of Ga complexes and to follow the purification steps of the Ga complex solutions. Copyright © 2011 John Wiley & Sons, Ltd.

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“…The awareness about the problem is stimulating researchers towards the synthesis of new Gd complexes with a fast water exchange, a high water relaxivity and a very good stability versus zinc transmetallation [7].…”

Section: Gadolinium (Gd)mentioning

confidence: 99%