High Relaxivity Confined to a Small Molecular Space: A Metallostar‐Based, Potential MRI Contrast Agent

Livramento, João Bruno; Tóth, Éva; Sour, Angélique; Borel, Alain; Merbach, André E.; Ruloff, Robert

doi:10.1002/ange.200461875

Cited by 36 publications

(47 citation statements)

References 9 publications

(10 reference statements)

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“…For example, the TTAHA (N-bis(2-aminoethyl)amine-N',N',N'',N''-tetraacetate) based metallostar has a relaxivity of 32 mM -1 s -1 at 20 MHz. [90] To test the approach of true self-assembly, HOPO-TAM mixed ligands have been investigated, using a C3 linker between the TAM (terephthalamide) and the HOPO chelates (32, Figure 11). [68] The assembly reduces the tumbling of the incorporated Gd-complexes in solution, and the resulting longer rotational correlation time afforded higher relaxivities of 18.7 mM -1 s -1 and 23 mM -1 s -1 at 20 and 60…”

Section: Fe/gd Supramolecular Complexesmentioning

confidence: 99%

High‐Relaxivity MRI Contrast Agents: Where Coordination Chemistry Meets Medical Imaging

et al. 2008

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Section: Fe/gd Supramolecular Complexesmentioning

confidence: 99%

High‐Relaxivity MRI Contrast Agents: Where Coordination Chemistry Meets Medical Imaging

et al. 2008

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“…Indeed, this compound represents the most concentrated paramagnetic relaxation effect among all Gd III -based potential contrast agents ever reported (4).…”

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confidence: 99%

Firstin vivo MRI assessment of a self-assembled metallostar compound endowed with a remarkable high field relaxivity

Livramento

Weidensteiner

Prata

et al. 2006

Contrast Media Mol Imaging

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À ¼ GdDOTA). The metallostar was well tolerated by the animals at the concentrations of 0.0500 (high dose) and 0.0125 (low dose) mmol Gd kg À1 body weight; (BW). The signal enhancement in the inversion recovery fast low angle shot (IR FLASH) images after the high-dose metallostar injection was considerably higher than after GdDOTA injection (0.1 mmol Gd kg À1 BW), despite the higher dose of the latter. The high-dose metallostar injection resulted in a greater drop in the spin-lattice relaxation time (T 1 ), as calculated from the inversion recovery true fast imaging with steady-state precession (IR TrueFISP) data for various tissues, than the GdDOTA or the low dose metallostar injection. In summary, these studies have confirmed that the approximately four times higher relaxivity measured in vitro for the metallostar is retained under in vivo conditions. The pharmacokinetics of the metallostar was found to be similar to that of GdDOTA, involving fast renal clearance, a leakage to the extracellular space in the muscle tissue and no leakage to the brain. As expected on the basis of its moderate molecular weight, the metallostar does not function as a blood pool agent. The dynamic g scintigraphic studies performed in Wistar rats with the metallostar compound having 153 Sm enrichment also proved the renal elimination pathway. The biodistribution experiments are in full accordance with the MR and scintigraphic imaging. At 15 min post-injection the activity is primarily localized in the urine, while at 24 h post-injection almost all radioactivity is cleared from tissues and organs.

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“…The former shows an increase of about 200% at 40 MHz on the formation of the heterobimetallic complex (metallostar), giving rise to an exceptionally high relaxivity confined to a small molecular space. 39,40 This high in vitro relaxivity is retained under in vivo conditions in mice. The pharmacokinetics of this metallostar, injected intravenously, were found to be similar to that of Gd-DOTA, involving fast renal clearance and a leakage to the extracellular space in the muscle tissue.…”

Section: Fe Sensingmentioning

confidence: 95%

Smart MR Imaging Agents Relevant to Potential Neurologic Applications

Bonnet¹,

Tóth²

2009

AJNR Am J Neuroradiol

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SUMMARY: Molecular imaging is aimed at the noninvasive visualization of the expression and function of bioactive molecules that often represent specific molecular signatures in disease processes. Any molecular imaging procedure requires an imaging probe that is specific to a given molecular event, which puts an important emphasis on chemistry development. In MR imaging, the past years have witnessed significant advances in the design of molecular agents, though most of these efforts have not yet progressed to in vivo studies. In this review, we present some examples relevant to potential neurobiologic applications. Our aim was to show what chemistry can bring to the area of molecular MR imaging with a focus on the 2 main classes of imaging probes: Gd 3ϩ -based and PARACEST agents. We will discuss responsive probes for the detection of metal ions such as Ca, Zn, Fe, and Cu, pH, enzymatic activity, and oxygenation state.ABBREVIATIONS: BBB ϭ blood-brain barrier; BOLD ϭ blood oxygen levelϪdependent; bpy ϭ bipyridine; C, carbon; Ca ϭ calcium; CEST ϭ chemical exchange saturation transfer; CO 3 ϭ carbonate; Cu ϭ copper; DTPA ϭ diethylene-triamine pentaacetic acid; DOTA ϭ 1,4,7,10-tetraaza-1,4,7,10-tetrakis(carboxymethyl)cyclododecane; Eu ϭ europium; Fe ϭ iron; Gd ϭ gadolinium; H ϭ hydrogen; HSA ϭ human serum albumin; k ex ϭ exchange rate; M ϭ metal ion; Mn ϭ manganese; N ϭ nitrogen; O ϭ oxygen; OH ϭ hydroxide; PARACEST ϭ paramagnetic CEST; PO 4 ϭ phosphate; q ϭ number of water molecules coordinated to Gd 3ϩ ; T 1,2e ϭ electron spin relaxation times; TPEN ϭ N,N,NЈ,NЈ-tetrakis(2-pyridylmethyl)ethylene-diamine; tpps ϭ 5,10,15,20-tetrakis-(p-sulfonatophenyl porphinate; tpy ϭ terpyridine; Yb ϭ ytterbium; Zn ϭ zinc; tau R ϭ reorientational correlation time of the molecule M olecular imaging is an emerging science area aimed at noninvasive visualization of the expression and function of bioactive molecules that often represent specific molecular signatures in disease processes. It seeks the biochemical or physiologic abnormalities underlying the disease, rather than the structural consequences of these abnormalities. Potential clinical applications of molecular imaging have been widely recognized, though the limited sensitivity and specificity of current molecular imaging approaches are often a major roadblock for clinical applications. Besides clinical settings, drug development can also largely benefit from the integration of molecular imaging. Molecular imaging not only allows rationalization of the parameters related to disease processes but it can also replace the common invasive research techniques (such as histology, which requires sacrificing animals for each time point in the experiment) by time-effective repeatable real-time visualization of biologically relevant processes. Currently, progress in the molecular imaging area is simultaneously moving at 3 levels: 1) improving the imaging hardware for use in preclinical and clinical settings, 2) identifying and validating new biologically relevant imaging targets, and 3...

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High Relaxivity Confined to a Small Molecular Space: A Metallostar‐Based, Potential MRI Contrast Agent

Cited by 36 publications

References 9 publications

High‐Relaxivity MRI Contrast Agents: Where Coordination Chemistry Meets Medical Imaging

High‐Relaxivity MRI Contrast Agents: Where Coordination Chemistry Meets Medical Imaging

Firstin vivo MRI assessment of a self-assembled metallostar compound endowed with a remarkable high field relaxivity

Smart MR Imaging Agents Relevant to Potential Neurologic Applications

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