Contrast-enhanced Blood-Pool MR Angiography with Optimized Iron Oxides: Effect of Size and Dose on Vascular Contrast Enhancement in Rabbits

Allkemper, Thomas; Bremer, Christoph; Matuszewski, Lars; Ebert, Wolfgang; Reimer, Peter

doi:10.1148/radiol.2232010241

Cited by 113 publications

(84 citation statements)

References 48 publications

(51 reference statements)

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“…Nevertheless, the possibility of spontaneous dissolution of nanoparticles generating highly toxic free iron(III) ions can be ruled out considering the low solubility of iron oxides, and also the presence of proteins with many high affinity active sites for bonding iron such as ferritin and hemosiderin. Probably, cat-USPIOs is being uptaken (phagocytosed or endocytosed) by reticuloendothelial system 28 of liver (mainly endothelial and Kupffer cells) and compartmentalized within lysosomes, where they are broken down due to low pH (3.5-4.0). The breakdown products as ferritin and hemosiderin exhibit magnetization tenfold lower than cat-USPIOs.…”

Section: Cationic Uspios As Mri Contrast Agent and Magnetic-targetingmentioning

confidence: 99%

Ultrasmall cationic superparamagnetic iron oxide nanoparticles as nontoxic and efficient MRI contrast agent and magnetic-targeting tool

Uchiyama¹,

Toma²,

Rodrigues³

et al. 2015

IJN

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Fully dispersible, cationic ultrasmall (7 nm diameter) superparamagnetic iron oxide nanoparticles, exhibiting high relaxivity (178 mM −1 s −1 in 0.47 T) and no acute or subchronic toxicity in Wistar rats, were studied and their suitability as contrast agents for magnetic resonance imaging and material for development of new diagnostic and treatment tools demonstrated. After intravenous injection (10 mg/kg body weight), they circulated throughout the vascular system causing no microhemorrhage or thrombus, neither inflammatory processes at the mesentery vascular bed and hepatic sinusoids (leukocyte rolling, adhesion, or migration as evaluated by intravital microscopy), but having been spontaneously concentrated in the liver, spleen, and kidneys, they caused strong negative contrast. The nanoparticles are cleared from kidneys and bladder in few days, whereas the complete elimination from liver and spleen occurred only after 4 weeks. Ex vivo studies demonstrated that cationic ultrasmall superparamagnetic iron oxide nanoparticles caused no effects on hepatic and renal enzymes dosage as well as on leukocyte count. In addition, they were readily concentrated in rat thigh by a magnet showing its potential as magnetically targeted carriers of therapeutic and diagnostic agents. Summarizing, cationic ultrasmall superparamagnetic iron oxide nanoparticles are nontoxic and efficient magnetic resonance imaging contrast agents useful as platform for the development of new materials for application in theranostics.

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Section: Cationic Uspios As Mri Contrast Agent and Magnetic-targetingmentioning

confidence: 99%

Ultrasmall cationic superparamagnetic iron oxide nanoparticles as nontoxic and efficient MRI contrast agent and magnetic-targeting tool

Uchiyama¹,

Toma²,

Rodrigues³

et al. 2015

IJN

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“…RESOVIST allows a potential improvement in diagnostic capability compared with the first-generation SPIO CAs such as ferumoxide (ENDOREM Guerbet, Aulnay-sous-Bois, France, and Feridex). Due to a large distributed particle size, ranging from 21-60 nm (1,2), the mean hydrodynamic diameter of ferucarbotran is smaller than that of ferumoxide particles, 60 versus 150 nm, respectively. Particles are coated with carboxydextran (rather than dextran, as in ferumoxide) which ensures aqueous solubility and prevents aggregation.…”

Section: Ferucarbotran (Resovist Shu 555 a Bayermentioning

confidence: 99%

Superparamagnetic iron oxide‐enhanced liver MRI with SHU 555 A (RESOVIST®): New protocol infusion to improve arterial phase evaluation—A prospective study

Grazioli¹,

Bondioni²,

Romanini³

et al. 2009

Magnetic Resonance Imaging

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Purpose:To compare the arterial enhancement of hypervascular hepatic lesions by T1-weighted 3D-GRE (gradientrecalled echo) fat-sat sequence after slow (0.5 mL/sec) and fast (2 mL/sec) RESOVIST infusion. Materials and Methods:We prospectively enrolled 71 patients with hypervascular hepatic lesions to undergo dynamic magnetic resonance imaging (MRI) examination with RESOVIST. A total of 92 benign and malignant lesions, 44 of which histologically confirmed, were examined. Three blinded and independent readers visually assessed the arterial enhancement using a score from 0 (none) to 3 (maximum), the latter score comparable to that achievable by MultiHance administration. Results:Out of the 92 hypervascular lesions, 41, 31, and 20 nodules were examined using the slow, fast, and both protocols, respectively. Relevant enhancement (scores 2-3) was found in 42% vs. 14.5% of cases for slow and fast protocols, respectively. Intraindividual comparison evaluation confirmed the better results obtained by slow than fast protocol (25% vs. 10%), with statistically relevant difference in distribution of scores (P ϭ 0.0004). The slow protocol showed values between 0 and 3 with an arithmetic mean of 1.1; the fast one, on the other hand, showed values between 0 and 2 with an arithmetic mean of 0.66. Conclusion FERUCARBOTRAN (RESOVIST, SHU 555 A, BayerSchering Pharma, Berlin, Germany) is a contrast agent (CA) composed of superparamagnetic iron oxide (SPIO) particles. RESOVIST allows a potential improvement in diagnostic capability compared with the first-generation SPIO CAs such as ferumoxide (ENDOREM Guerbet, Aulnay-sous-Bois, France, and Feridex). Due to a large distributed particle size, ranging from 21-60 nm (1,2), the mean hydrodynamic diameter of ferucarbotran is smaller than that of ferumoxide particles, 60 versus 150 nm, respectively. Particles are coated with carboxydextran (rather than dextran, as in ferumoxide) which ensures aqueous solubility and prevents aggregation.Ferumoxide is infused slowly to avoid lumbar pain and hypotensive reaction. Conversely, RESOVIST does not cause side effects after rapid intravenous injection, therefore allowing dynamic examination and, similar to ferumoxide, reticulo-endothelial system (RES) specific imaging in the delayed phase (3). RESOVIST is taken up by phagocytic Kupffer cells of the liver (80%), spleen (8%-10%) (4), bone marrow, and lymph nodes (10%). Following uptake by Kupffer cells, a decrease in signal intensity (SI) can be seen in tissues that take up RESO-VIST (5). Generally, iron oxide particles are used as negative enhancers because they have a high R 2 /R 1 relaxivity ratio, meaning that the effect on T2 shortening is generally much stronger than that on T1 shortening. As the particles are taken up by Kupffer cells in the liver, the T2 effect becomes the dominant mechanism due to accumulation of the CA at higher concentrations. Therefore, RESOVIST induces a decrease in SI in lesions that contain phagocytic cells (benign lesions) or a significant blood-pool (hemangiomas) on T2-

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“…8 In general, smaller particles circulate for longer than larger particles, and can be gradually taken up by the reticuloendothelial system in lymph tissue and bone marrow. [8][9][10][11][12][13] Larger particles over 50 nm are generally taken up quickly by the reticuloendothelial system in Kupffer cells of the liver, and have limited uptake in lymph and bone tissues. 6 The coating material rather than the mean hydrated size of the iron oxide particle contributes significantly to the rate of iron oxide particle clearance and degradation in sinusoidal Kupffer liver cells, especially for particles smaller than 40 nm in diameter.…”

Section: Introductionmentioning

confidence: 99%

Metabolic pathway and distribution of superparamagnetic iron oxide nanoparticles: in vivo study

Schlachter

Widmer²,

Bregy³

et al. 2011

IJN

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Background: Experimental tissue fusion benefits from the selective heating of superparamagnetic iron oxide nanoparticles (SPIONs) under high frequency irradiation. However, the metabolic pathways of SPIONs for tissue fusion remain unknown. Hence, the goal of this in vivo study was to analyze the distribution of SPIONs in different organs by means of magnetic resonance imaging (MRI) and histological analysis after a SPION-containing patch implantation. Methods: SPION-containing patches were implanted in rats. Three animal groups were studied histologically over six months. Degradation assessment of the SPION-albumin patch was performed in vivo using MRI for iron content localization and biodistribution. Results: No SPION degradation or accumulation into the reticuloendothelial system was detected by MRI, MRI relaxometry, or histology, outside the area of the implantation patch. Concentrations from 0.01 µg/mL to 25 µg/mL were found to be hyperintense in T1-like gradient echo sequences. The best differentiation of concentrations was found in T2 relaxometry, susceptibility-sensitive gradient echo sequences, and in high repetition time T2 images. Qualitative and semiquantitative visualization of small concentrations and accumulation of SPIONs by MRI are feasible. In histological liver samples, Kupffer cells were significantly correlated with postimplantation time, but no differences were observed between sham-treated and induction/no induction groups. Transmission electron microscopy showed local uptake of SPIONs in macrophages and cells of the reticuloendothelial system. Apoptosis staining using caspase showed no increased toxicity compared with sham-treated tissue. Implanted SPION patches were relatively inert with slow, progressive local degradation over the six-month period. No distant structural alterations in the studied tissue could be observed. Conclusion: Systemic bioavailability may play a role in specific SPION implant toxicity and therefore the local degradation process is a further aspect to be assessed in future studies.

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Contrast-enhanced Blood-Pool MR Angiography with Optimized Iron Oxides: Effect of Size and Dose on Vascular Contrast Enhancement in Rabbits

Abstract: The smallest iron oxide provided signal enhancement comparable with that of gadopentetate dimeglumine at 40 micromol iron per kilogram for first-pass investigations, with prolonged signal enhancement up to 25 minutes, allowing multiple measurements after injection of a single bolus.

Cited by 113 publications

References 48 publications

Ultrasmall cationic superparamagnetic iron oxide nanoparticles as nontoxic and efficient MRI contrast agent and magnetic-targeting tool

Ultrasmall cationic superparamagnetic iron oxide nanoparticles as nontoxic and efficient MRI contrast agent and magnetic-targeting tool

Superparamagnetic iron oxide‐enhanced liver MRI with SHU 555 A (RESOVIST®): New protocol infusion to improve arterial phase evaluation—A prospective study

Metabolic pathway and distribution of superparamagnetic iron oxide nanoparticles: in vivo study

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