MS-325: albumin-targeted contrast agent for MR angiography.

Lauffer, Randall B.; Parmelee, David J.; Dunham, Stephen U.; Ouellet, Hillori S.; Dolan, Robert; Witte, S; McMurry, Thomas J.; Walovitch, Richard C.

doi:10.1148/radiology.207.2.9577506

Cited by 447 publications

(355 citation statements)

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“…Furthermore, as PC-MRA is sensitive to the available signal-to-noise ratio (SNR), contrast agents may help to enhance vessel surface extraction and 3D flow visualization (26)(27)(28).…”

Section: Contrast-enhanced (Ce) Mr Angiography (Mra) Is An Establishementioning

confidence: 99%

4D phase contrast MRI at 3 T: Effect of standard and blood‐pool contrast agents on SNR, PC‐MRA, and blood flow visualization

Bock

Frydrychowicz

Stalder

et al. 2009

Magnetic Resonance in Med

159

117

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Time-resolved phase contrast (PC) MRI with velocity encoding in three directions (flow-sensitive four-dimensional MRI) can be employed to assess three-dimensional blood flow in the entire aortic lumen within a single measurement. These data can be used not only for the visualization of blood flow but also to derive additional information on vascular geometry with three-dimensional PC MR angiography (MRA). As PC-MRA is sensitive to available signal-to-noise ratio, standard and novel blood pool contrast agents may help to enhance PC-MRA image quality. In a group of 30 healthy volunteers, the influence of different contrast agents on vascular signalto-noise ratio, PC-MRA quality, and subsequent three-dimensional stream-line visualization in the thoracic aorta was determined. Flow-sensitive four-dimensional MRI data acquired with contrast agent provided significantly improved signal-to-noise ratio in magnitude data and noise reduction in velocity data compared to measurements without contrast media. The agreement of three-dimensional PC-MRA with reference standard contrast-enhanced MRA was good for both contrast agents, with improved PC-MRA performance for blood pool contrast agent, particularly for the smaller supraaortic branches. While most clinical applications of MRA rely on the application of Gadolinium (Gd) contrast agent (CA), three-dimensional (3D) phase contrast (PC)-MRA based on velocity-encoded 3D MRI with encoding in three directions has proven to be a useful alternative (8-11). PC-MRA can provide detailed information on vascular geometry and may offer additional information on flow direction. However, most PC-MRA implementations used nongated data acquisition, which can result in artifacts for pulsatile blood flow. Further drawbacks of the PC-MRA method are long scan times and lack of respiration control, which limited most applications of 3D PC-MRA to static regions with low pulsatile flow such as the cranial vessels (12,13).Recently, improved time-resolved (CINE) 3D PC MRI techniques using electrocardiography (ECG) gating and advanced navigator respiration control (flow-sensitive four-dimensional [4D] MRI) have been successfully applied for the analysis of pulsatile 3D blood flow in the aorta (14-24). Such techniques offer the opportunity for the detailed analysis of pulsatile 3D blood flow but require scan times up to 20 min. We previously reported an approach to derive 3D angiographic information (3D PC-MRA) from flow-sensitive 4D MRI (24,25). We showed that it was possible to exploit the information in the acquired flow-sensitive 4D data to derive angiographic information without performing additional MRA measurements. Although the derived 3D PC-MRA does not provide the same detailed depiction of anatomy and morphology compared to CE-MRA, it can improve considerably the presentation of the results by combining 3D visualization of anatomy and flow for large vascular geometries such as the thoracic aorta.Based on this strategy, an improved data processing workflow including noise masking was impleme...

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“…Furthermore, as PC-MRA is sensitive to the available signal-to-noise ratio (SNR), contrast agents may help to enhance vessel surface extraction and 3D flow visualization (26)(27)(28).…”

Section: Contrast-enhanced (Ce) Mr Angiography (Mra) Is An Establishementioning

confidence: 99%

4D phase contrast MRI at 3 T: Effect of standard and blood‐pool contrast agents on SNR, PC‐MRA, and blood flow visualization

Bock

Frydrychowicz

Stalder

et al. 2009

Magnetic Resonance in Med

159

117

View full text Add to dashboard Cite

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“…Consequently, there is considerable interest in the use of blood pool (also called intravascular) agents for contrast-enhanced MRA. Various blood pool agents have been tested, including gadolinium-based and ultrasmall superparamagnetic iron oxide (USPIO)-based agents (3)(4)(5)(6)(7)(8)(9). Compared with extracellular agents, blood pool agents provide a much longer time window for data acquisition, so that data can be repeatedly acquired over a period of minutes to hours with little loss of intravascular signal intensity.…”

mentioning

confidence: 99%

First‐pass contrast‐enhanced magnetic resonance angiography in humans using ferumoxytol, a novel ultrasmall superparamagnetic iron oxide (USPIO)‐based blood pool agent

Li¹,

Tutton²,

Vu³

et al. 2004

Magnetic Resonance Imaging

207

139

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Purpose:To evaluate the feasibility of first-pass contrastenhanced magnetic resonance angiography (MRA) using ferumoxytol in humans. Materials and Methods:First-pass and equilibrium phase MRA were performed using ferumoxytol in one healthy volunteer and 11 patients with a fast three-dimensional spoiled gradient recalled (SPGR) pulse sequence. The examined vessels included carotid arteries, thoracic aorta, abdominal aorta, and peripheral arteries. A dose of either 71.6 mol Fe/kg (n ϭ 9), or 35.8 mol Fe/kg (n ϭ 3) was used. Based on a phantom study, the agent with initial concentration of 537.2 mol Fe/mL was diluted by either four-fold (134.3 mol Fe/mL) or eight-fold (67.1 mol Fe/ mL) for first-pass MRA.Results: All subjects completed their studies without adverse events. First-pass MRA showed selective arterial enhancement, with both arterial and venous enhancement on delayed acquisitions. Selective venous enhancement could be obtained by subtraction of arterial phase images from equilibrium phase images. The findings in ferumoxytol MRA were consistent with the results of original vascular tests. Conclusion:Our preliminary experience supports the feasibility of first-pass MRA with ferumoxytol. Satisfactory arterial enhancement during first-pass imaging is obtained with injection of diluted contrast agent. With ferumoxytol, arteries and veins can be selectively depicted in a single exam.

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“…6, 10 The hydrophobic interaction between their gadolinium chelate and the plasma protein led to a substantial increase in the longitudinal relaxivity upon binding to the protein. However, the binding between their gadolinium-based MRI contrast agent and the plasma protein was rather weak and non-specific.…”

mentioning

confidence: 99%

Probing the interaction of the biotin–avidin complex with the relaxivity of biotinylated Gd-DTPA

et al. 2004

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A biotinylated Gd-DTPA complex is designed to study the biotin-avidin complexation using the longitudinal relaxivity of this new MRI label, which illustrates the use of MRI contrast agents to probe the formation of supramolecular assemblies in water.Magnetic resonance imaging (MRI) contrast agents, such as the gadolinium complex of diethylenetriaminepentaacetic acid (Gd-DTPA), are commonly utilized to increase both the contrast and the anatomical detail of an MR image, due to their ability to enhance the longitudinal relaxation rate (R 1 = 1/T 1 ) of the protons of water molecules. 1-4 The efficiency of an MRI contrast agent is often expressed in terms of relaxivity (r), i.e. the change in relaxation rate divided by the concentration of MRI contrast agent in mM. Low molecular weight Gd-DTPA complexes have a relatively low relaxivity and a non-specific biodistribution. 4 It is well established that MRI contrast agents can bind to macromolecules, either in a covalent 2-4 or a noncovalent 4-9 fashion, which induces a pronounced enhancement of the relaxivity, due to a decrease in the molecular tumbling rate of the gadolinium complex. 4 As a result, the relaxivity can be utilized to probe molecular weight and/or the association process of Gd-DTPA structures.In a pioneering study of Lauffer et al., the non-covalent, reversible binding of low molecular weight MRI contrast agents to human serum albumin, a plasma protein, was described. 6,10 The hydrophobic interaction between their gadolinium chelate and the plasma protein led to a substantial increase in the longitudinal relaxivity upon binding to the protein. However, the binding between their gadolinium-based MRI contrast agent and the plasma protein was rather weak and non-specific. 6 Under such conditions the association process is complicated to study (multiple steps with different association constants). Lately, several exciting approaches in the development of MRI contrast agents with a higher specifity and an increased binding affinity have been reported, including enzyme-specific MRI contrast agents, 11 DNA-specific MRI contrast agents 12 and protein-specific MRI contrast agents. 13 To study the relation between the relaxivity and strong noncooperative binding of guests to a multivalent host in a quantitative manner, we developed an MRI contrast agent based on biotinylated Gd-DTPA, which can be associated with avidin ( Fig. 1). It is well established that avidin, a tetrameric protein, is capable of binding four equivalents of biotin in a strong, noncooperative fashion (K a ∼ 1.7 × 10 15 M Ϫ1 ). 14 The biotinylated Gd-DTPA complex 4 was synthesized via a three-step procedure (Scheme 1). The intermediate products 2 and 3 were characterized with 1 H-NMR spectroscopy, IR spectroscopy, and ES-QTOF-MS. The formation of the gadolinium complex 4 was confirmed with IR spectroscopy and † Electronic supplementary information (ESI) available: further results and experimental details. See http://www.rsc.org/suppdata/ob/b4/ b402917h/ ES-QTOF-MS, while the gadolinium content...

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MS-325: albumin-targeted contrast agent for MR angiography.

Abstract: MS-325 is highly protein bound after injection and provides vascular signal enhancement superior to that provided with other agents. As the first gadolinium-based blood pool agent in human trials, MS-325 has the potential to enhance both dynamic and steady-state MR angiograms.

Cited by 447 publications

References 0 publications

4D phase contrast MRI at 3 T: Effect of standard and blood‐pool contrast agents on SNR, PC‐MRA, and blood flow visualization

4D phase contrast MRI at 3 T: Effect of standard and blood‐pool contrast agents on SNR, PC‐MRA, and blood flow visualization

First‐pass contrast‐enhanced magnetic resonance angiography in humans using ferumoxytol, a novel ultrasmall superparamagnetic iron oxide (USPIO)‐based blood pool agent

Probing the interaction of the biotin–avidin complex with the relaxivity of biotinylated Gd-DTPA

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