Next Generation, High Relaxivity Gadolinium MRI Agents

Raymond, Kenneth N.; Pierre, Valérie C.

doi:10.1021/bc049817y

Cited by 310 publications

(283 citation statements)

References 33 publications

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“…T 1e can be estimated from Δ 2 and τ V to be significantly longer than for other HOPO chelates reported. 11 Thus T 1e and τ M represent optimal values for a significant improvement of r 1p to over 100 mM −1 s −1 by slowing rotational tumbling (Figure 2). …”

Section: Resultsmentioning

confidence: 89%

Optimized Relaxivity and Stability of [Gd(H(2,2)-1,2-HOPO)(H₂O)]^- for Use as an MRI Contrast Agent¹

et al. 2007

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Relaxometry and solution thermodynamic measurements show that Gd-H(2,2)-1,2-HOPO is a good candidate as a contrast agent for Magnetic Resonance Imaging (MRI-CA). Acidic, octadentate H(2,2)-1,2-HOPO forms a very stable Gd(III) complex [pGd 21.2 (2)]. The coordination sphere at the Gd(III) center is completed by one water molecule that is not replaced by common physiological anions. In addition, this ligand is highly selective for Gd(III) binding in the presence of Zn(II) or Ca(II).The symmetric charge distribution of the 1,2-HOPO chelates is associated with favorably long electronic relaxation time T 1,2e comparable to those of GdDOTA. This, in addition to the fast water exchange rate typical of HOPO chelates improves relaxivity to r 1p = 8.2 mM −1 s −1 (0.47 T). This remarkably high value is unprecedented for small molecule, q = 1 MRI-CA.

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Section: Resultsmentioning

confidence: 89%

Optimized Relaxivity and Stability of [Gd(H(2,2)-1,2-HOPO)(H₂O)]^- for Use as an MRI Contrast Agent¹

et al. 2007

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“…Additionally, Gd(III) may be promising as materials for simultaneous oxygen and magnetic resonance imaging, which is by far the most important application of the non-emissive Gd(III) chelates. [56][57] [58] In this contribution we will present a series of new Eu(III) and Gd(III) complexes which combine efficient excitation in the blue part of the electromagnetic spectrum, strong emission and efficient quenching by molecular oxygen. It will be shown that 9-hydroxy-1H-phenalen-1-one, in contrast to an early report, [59] represents an efficient antenna for sensitizing luminescence of the lanthanides under visible light and thus represents an excellent choice for preparation of high-performance optical materials.…”

Section: Introductionmentioning

confidence: 99%

Exceptional Oxygen Sensing Properties of New Blue Light‐Excitable Highly Luminescent Europium(III) and Gadolinium(III) Complexes

Borisov

Fischer

Saf

et al. 2014

Adv Funct Materials

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New europium(III) and gadolinium(III) complexes bearing 8-hydroxyphenalenone antenna combine efficient absorption in the blue part of the spectrum and strong emission in polymers at room temperature. The Eu(III) complexes show characteristic red luminescence whereas the Gd(III) dyes are strongly phosphorescent. The luminescence quantum yields are about 20% for the Eu(III) complexes and 50% for the Gd(III) dyes. In contrast to most state-of-the-art Eu(III) complexes the new dyes are quenched very efficiently by molecular oxygen. The luminescence decay times of the Gd(III) complexes exceed 1 ms which ensures exceptional sensitivity even in polymers of moderate oxygen permeability. These sensors are particularly suitable for trace oxygen sensing and may be good substitutes for Pd(II) porphyrins. The photophysical and sensing properties can be tuned by varying the nature of the fourth ligand. The narrow-band emission of the Eu(III) allows efficient elimination of the background light and autofluorescence and is also very attractive for use e.g. in multi-analyte sensors. The highly photostable indicators incorporated in nanoparticles are promising for imaging applications. Due to the straightforward preparation and low cost of starting materials the new dyes represent a promising alternative to the state-ofthe-art oxygen indicators particularly for such applications as e.g. food packaging.

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“…Although the hypothesis that both conjugated complexes possess q=1 cannot be excluded on the basis of the relaxometric data, the assumption of two bound water molecules gave the best fits (Supporting information Figure S1) for both the internally and externally modified capsids, and is consistent with other TREN-bis-HOPO-TAM derivatives. 7,30 The distance of the coordinated water molecules from the metal ion (r Gd-H ) was fixed to 3.1 Å. 40 Based on the observed relaxivity dependence with temperature and on the analogy with other Gd-TREN-bis-HOPO-TAM derivatives, the mean residence lifetime τ M was fixed to 10 ns (Supporting information Figures S2 and S3).…”

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confidence: 99%

“…The reason for the relaxivity enhancements observed can then be attributed to the optimal water exchange rates (in addition to the slow rotational correlation times) for the Gd-HOPO based systems, which would also lead to improved relaxivities for these macromolecular contrast agents at higher field strengths when compared to Gd-DOTA based system. 7,42 The NMRD profiles and the temperature dependence studies of these capsid systems indicate that they can be further improved to provide systems with sufficiently high relaxivity for biomarker targeting. Theoretical predictions for these systems (Figure 7) indicate that upon increasing the local reorientation correlation through the use of more rigid linkers, the relaxivity values can be increased to 140 mM -1 s -1 per Gd 3+ ion at clinically relevant fields.…”

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High Relaxivity Gadolinium Hydroxypyridonate−Viral Capsid Conjugates: Nanosized MRI Contrast Agents¹

et al. 2008

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High relaxivity macromolecular contrast agents based on the conjugation of gadolinium chelates to the interior and exterior surfaces of MS2 viral capsids are assessed. The proton nuclear magnetic relaxation dispersion (NMRD) profiles of the conjugates show up to a five-fold increase in relaxivity, leading to a peak relaxivity (per Gd 3+ ion) of 41.6 mM -1 s -1 at 30 MHz for the internally modified capsids. Modification of the exterior was achieved through conjugation to flexible lysines, while internal modification was accomplished by conjugation to relatively rigid tyrosines. Higher relaxivities were obtained for the internally modified capsids, showing that (i) there is facile diffusion of water to the interior of capsids and (ii) the rigidity of the linker attaching the complex to the macromolecule is important for obtaining high relaxivity enhancements. The viral capsid conjugated gadolinium hydroxypyridonate complexes appear to possess two inner-sphere water molecules (q = 2) and the NMRD fittings highlight the differences in the local motion for the internal (τ Rl = 440 ps) and external (τ Rl = 310 ps) conjugates. These results indicate that there are significant advantages of using the internal surface of the capsids for contrast agent attachment, leaving the exterior surface available for the installation of tissue targeting groups. MANUSCRIPT TEXTMagnetic resonance imaging (MRI) is a routinely used noninvasive diagnostic technique, providing detailed images without the use of ionizing radiation. Although the resolution of MRI is excellent, its dynamic range is relatively narrow because of the limited variation in relaxation rates exhibited by water protons in vivo. When these differences are insufficient to distinguish between adjacent tissues, contrast enhancement is often achieved through the administration of synthetic agents that increase the water proton relaxation rates in accessible locations. Gadolinium complexes are the most often used for this purpose, with more than 10 million MRI studies being performed through their use each year. [2][3][4] The current commercially available Gd(III)-based contrast agents use poly(aminocarboxylate) chelates, and typically gram quantities of Gd must be injected to reach concentrations sufficient for usable contrast enhancement. However, this strategy is more difficult to apply to the specific imaging of biomarkers present in low (μM -nM) concentrations. To distinguish these sites from the background signal, targetable contrast agents will undoubtedly require significantly improved contrast enhancement efficiencies. 3,5 2 MRI contrast agents are commonly evaluated on the basis of relaxivity (r 1p ), which describes their ability to increase the longitudinal relaxation rate of nearby water molecule protons per millimolar concentration of agent applied. 6 Strategies for enhancing the relaxivity of contrast agents include increasing the number of bound water molecules (q), optimizing the water-residence time (τ M ) and increasing the rotational correlati...

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Next Generation, High Relaxivity Gadolinium MRI Agents

Cited by 310 publications

References 33 publications

Optimized Relaxivity and Stability of [Gd(H(2,2)-1,2-HOPO)(H₂O)]^- for Use as an MRI Contrast Agent¹

Optimized Relaxivity and Stability of [Gd(H(2,2)-1,2-HOPO)(H₂O)]^- for Use as an MRI Contrast Agent¹

Exceptional Oxygen Sensing Properties of New Blue Light‐Excitable Highly Luminescent Europium(III) and Gadolinium(III) Complexes

High Relaxivity Gadolinium Hydroxypyridonate−Viral Capsid Conjugates: Nanosized MRI Contrast Agents¹

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Next Generation, High Relaxivity Gadolinium MRI Agents

Cited by 310 publications

References 33 publications

Optimized Relaxivity and Stability of [Gd(H(2,2)-1,2-HOPO)(H2O)]- for Use as an MRI Contrast Agent1

Optimized Relaxivity and Stability of [Gd(H(2,2)-1,2-HOPO)(H2O)]- for Use as an MRI Contrast Agent1

Exceptional Oxygen Sensing Properties of New Blue Light‐Excitable Highly Luminescent Europium(III) and Gadolinium(III) Complexes

High Relaxivity Gadolinium Hydroxypyridonate−Viral Capsid Conjugates: Nanosized MRI Contrast Agents1

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Optimized Relaxivity and Stability of [Gd(H(2,2)-1,2-HOPO)(H₂O)]^- for Use as an MRI Contrast Agent¹

Optimized Relaxivity and Stability of [Gd(H(2,2)-1,2-HOPO)(H₂O)]^- for Use as an MRI Contrast Agent¹

High Relaxivity Gadolinium Hydroxypyridonate−Viral Capsid Conjugates: Nanosized MRI Contrast Agents¹