Application of arsenazo III in the preparation and characterization of an albumin-linked, gadolinium-based macromolecular magnetic resonance contrast agent

Nagaraja, Tavarekere N.; Croxen, Richard L.; Panda, Swayamprava; Knight, Robert A.; Keenan, Kelly A.; Brown, Stephen L.; Fenstermacher, Joseph D.; Ewing, James R.

doi:10.1016/j.jneumeth.2006.05.013

Cited by 29 publications

(30 citation statements)

References 38 publications

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“…At 7 T and 25°C, a 20% solution of Gd-BSA exhibited T 1 and T 2 times of 128.3 and 48.9 ms, respectively, whereas Gd-DTPA gave T 1 and T 2 times of 33.2 and 32.6 ms, respectively, at a comparable concentration. 18 All 7 rats lost some body weight during the 24-hour poststroke period. Average weight at surgery was 298Ϯ15 g and at 24 hours after the ictus, 258Ϯ11 g. The CBF I/C values in the stroke-affected brain regions were 0.64Ϯ0.15 in the Gd-DTPA-and 0.66Ϯ0.14 in the Gd-BSA-EB-enhancing areas (Pϭ0.62).…”

Section: Resultsmentioning

confidence: 97%

“…The contrast agents Gd-BSA and Gd-DTPA were synthesized and characterized. 17,18 The Gd-BSA preparation was then incubated with EB, an often-used, fluorescent, albumin-binding vital dye, and linked to it in a Gd-BSA/EB molar ratio of 1:7 to obtain Gd-BSA-EB. This additional step rendered the molecule with both paramagnetic and fluorescent properties and enabled direct comparison of MR images with those from fluorescence microscopy.…”

Section: Preparation and Characterization Of Mrcamentioning

confidence: 99%

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Identification of Variations in Blood-Brain Barrier Opening After Cerebral Ischemia by Dual Contrast-Enhanced Magnetic Resonance Imaging and T _1sat Measurements

Nagaraja

Karki

Ewing

et al. 2008

Stroke

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Background and Purpose-Variations in blood-brain barrier (BBB) opening after ischemia have been suggested by some tracer and magnetization transfer studies, although direct in vivo proof is still lacking. Contrast-enhanced magnetic resonance imaging (MRI) is also often used to visualize BBB damage in stroke. We hypothesized that MR contrast agents of different sizes enhance differently when BBB openings vary in size and that magnetization transfer alterations, measured by T 1 in the presence of off-resonance radiofrequency saturation (T 1sat ), in these regions reflect such differences. Methods-Male Wistar rats (Ϸ300 g, nϭ7) were subjected to 3 hours of suture occlusion of the middle cerebral artery followed by reperfusion. Status of the BBB at 24 hours after the ictus was assessed first by Gd-DTPA (554 Da) MRI and then by Gd-bovine serum albumin linked to Evans blue (Gd-BSA-EB; Ϸ68 kDa) MRI for contrast enhancement; T 1sat changes, cerebral blood flow, and blood-to-brain transfer constants (K i s) for the 2 contrast agents were measured. After MRI, rats were injected with fluorescent dextran and brains were studied by fluorescence microscopy. Results-The Gd-BSA-EB-enhancing areas were always smaller (147Ϯ80 pixels) than those for Gd-DTPA (308Ϯ204 pixels) and were contained within the latter. The difference between the 2 areas was significant (Pϭ0.024). Changes in T 1sat were larger in Gd-BSA-EB-enhancing areas (ipsilateral to contralateral [I/C]ϭ1.53Ϯ0.20) than in Gd-DTPAenhancing areas (I/Cϭ1.40Ϯ0.24, Pϭ0.005). The differences in cerebral blood flow values between the 2 regions were not significant (Pϭ0.62), but those for the K i values of the 2 tracers were different (Pϭ0.01 to 0.02). Excellent agreement between regions of Gd-BSA-EB enhancement and EB fluorescence was also observed. Conclusions-These results substantiate earlier reports of regional differences in BBB opening after stroke and provide the first in vivo evidence for this phenomenon. They also support the possible use of T 1sat in quantifying stroke-induced graded BBB damage in the absence of contrast-enhanced MRI. (Stroke. 2008;39:427-432.)

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Section: Resultsmentioning

confidence: 97%

Section: Preparation and Characterization Of Mrcamentioning

confidence: 99%

Identification of Variations in Blood-Brain Barrier Opening After Cerebral Ischemia by Dual Contrast-Enhanced Magnetic Resonance Imaging and T _1sat Measurements

Nagaraja

Karki

Ewing

et al. 2008

Stroke

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“…16 However, gadolinium in its chelated form is commonly used to improve tissue contrast in MRI and has been proven to be safe in patients with normal kidney function. Our data showed that there was no release of gadolinium from the NPs using either the arsenazo assay recommended by the National Characterization Laboratory (USA) or the ICP-MS. 17 Additional investigations by protoninduced X-ray emission confirm that the structural integrity of the NPs has shown further evidence that there is no release of rare earth elements. 18 …”

Section: Np Synthesis and Characterizationmentioning

confidence: 91%

Efficacy of radiosensitizing doped titania nanoparticles under hypoxia and preparation of an embolic microparticle

Morrison¹,

Rybak-Smith²,

Thompson

et al. 2017

IJN

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The aim of this study was to develop a manufacturing protocol for large-scale production of doped titania radiosensitizing nanoparticles (NPs) to establish their activity under hypoxia and to produce a multimodal radiosensitizing embolic particle for cancer treatment. We have previously shown that radiosensitizing NPs can be synthesized from titania doped with rare earth elements, especially gadolinium. To translate this technology to the clinic, a crucial step is to find a suitable, scalable, high-throughput method. Herein, we have described the use of flame spray pyrolysis (FSP) to generate NPs from titanium and gadolinium precursors to produce titania NPs doped with 5 at% gadolinium. The NPs were fully characterized, and their capacity to act as radiosensitizers was confirmed by clonogenic assays. The integrity of the NPs in vitro was also ascertained due to the potentially adverse effects of free gadolinium in the body. The activity of the NPs was then studied under hypoxia since this is often a barrier to effective radiotherapy. In vitro radiosensitization experiments were performed with both the hypoxia mimetics deferoxamine and cobalt chloride and also under true hypoxia (oxygen concentration of 0.2%). It was shown that the radiosensitizing NPs were able to cause a significant increase in cell death even after irradiation under hypoxic conditions such as those found in tumors. Subsequently, the synthesized NPs were used to modify polystyrene embolization microparticles. The NPs were sintered to the surface of the microparticles by heating at 230°C for 15 minutes. This resulted in a good coverage of the surface and to generate embolization particles that were shown to be radiosensitizing. Such multimodal particles could therefore result in occlusion of the tumor blood vessels in conjunction with localized reactive oxygen species generation, even under hypoxic conditions such as those found in the center of tumors.

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“…26 Briefly, samples were diluted 1:100 with HNO 3 solution (0.1 M HNO 3 , 10 mM urea, 0.1% Triton X-100, pH 1.0) to release gadolinium ions. Next, 500 µL of samples were mixed with 500 µL of arsenazo III (100 µg/mL) dissolved in the same buffer.…”

Section: Preparation Of Gadolinium-labeled Recombinant Hdl Nanoparticlesmentioning

confidence: 99%

Recombinant high-density lipoprotein nanoparticles containing gadolinium-labeled cholesterol for morphologic and functional magnetic resonance imaging of the liver

Rui

Guo²,

Ding³

et al. 2012

IJN

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Background: Natural high-density lipoproteins (HDL) possess important physiological functions to the transport of cholesterol from the peripheral tissues to the liver for metabolic degradation and excretion in the bile. Methods and results:In this work, we took advantage of this pathway and prepared two different gadolinium (Gd)-DTPA-labeled cholesterol-containing recombinant HDL nanoparticles (Gd-chol-HDL) and Gd-(chol) 2 -HDL as liver-specific magnetic resonance imaging (MRI) contrast agents. The reconstituted HDL nanoparticles had structural similarity to native HDL, and could be taken up by HepG2 cells via interaction with HDL receptors in vitro. In vivo MRI studies in rats after intravenous injections of 10 µmol gadolinium per kg of recombinant HDL nanoparticles indicated that both nanoparticles could provide signal enhancement in the liver and related organs. However, different T 1 -weighted image details suggested that they participated in different cholesterol metabolism and excretion pathways in the liver. Conclusion: Such information could be highly useful to differentiate functional changes as well as anatomic differences in the liver. These cholesterol-derived contrast agents and their recombinant HDL preparations may warrant further development as a new class of contrast agents for MRI of the liver and related organs.

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Application of arsenazo III in the preparation and characterization of an albumin-linked, gadolinium-based macromolecular magnetic resonance contrast agent

Cited by 29 publications

References 38 publications

Identification of Variations in Blood-Brain Barrier Opening After Cerebral Ischemia by Dual Contrast-Enhanced Magnetic Resonance Imaging and T _1sat Measurements

Identification of Variations in Blood-Brain Barrier Opening After Cerebral Ischemia by Dual Contrast-Enhanced Magnetic Resonance Imaging and T _1sat Measurements

Efficacy of radiosensitizing doped titania nanoparticles under hypoxia and preparation of an embolic microparticle

Recombinant high-density lipoprotein nanoparticles containing gadolinium-labeled cholesterol for morphologic and functional magnetic resonance imaging of the liver

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Application of arsenazo III in the preparation and characterization of an albumin-linked, gadolinium-based macromolecular magnetic resonance contrast agent

Cited by 29 publications

References 38 publications

Identification of Variations in Blood-Brain Barrier Opening After Cerebral Ischemia by Dual Contrast-Enhanced Magnetic Resonance Imaging and T 1sat Measurements

Identification of Variations in Blood-Brain Barrier Opening After Cerebral Ischemia by Dual Contrast-Enhanced Magnetic Resonance Imaging and T 1sat Measurements

Efficacy of radiosensitizing doped titania nanoparticles under hypoxia and preparation of an embolic microparticle

Recombinant high-density lipoprotein nanoparticles containing gadolinium-labeled cholesterol for morphologic and functional magnetic resonance imaging of the liver

Contact Info

Product

Resources

About

Identification of Variations in Blood-Brain Barrier Opening After Cerebral Ischemia by Dual Contrast-Enhanced Magnetic Resonance Imaging and T _1sat Measurements

Identification of Variations in Blood-Brain Barrier Opening After Cerebral Ischemia by Dual Contrast-Enhanced Magnetic Resonance Imaging and T _1sat Measurements