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 USPIO            Ultrasmall SuperParamagnetic Iron Oxide 
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Ultrasmall Superparamagnetic Iron OxideInfoSheet: - Contrast Agents - 
Intro, Overview, 
Characteristics, 
Types of, 
etc.
 
(USPIO) The class of the ultrasmall superparamagnetic iron oxide includes several chemically and pharmacologically very distinct materials, which may or may not be interchangeable for a specific use. Some ultrasmall SPIO particles (median diameter less than 50nm) are used as MRI contrast agents (Sinerem®, Combidex®), e.g. to differentiate metastatic from inflammatory lymph nodes. USPIO shows also potential for providing important information about angiogenesis in cancer tumors and could possibly complement MRI helping physicians to identify dangerous arteriosclerosis plaques.
Because of the disadvantageous large T2*//T1 ratio, USPIO compounds are less suitable for arterial bolus contrast enhanced magnetic resonance angiography than gadolinium complexes. The tiny ultrasmall superparamagnetic iron oxides do not accumulate in the RES system as fast as larger particles, which results in a long plasma half-life. USPIO particles, with a small median diameter (less than 10 nm), will accumulate in lymph nodes after an intravenous injection by e.g. direct transcapillary passage through endothelial venules. Once within the nodal parenchyma, phagocytic cells of the mononuclear phagocyte system take up the particles.
As a second way, USPIOs are subsequently taken up from then interstitium by lymphatic vessels and transported to regional lymph nodes. A lymph node with normal phagocytic function takes up a considerable amount and shows a reduction of the signal intensity caused by T2 shortening effects and magnetic susceptibility. Caused by the small uptake of the USPIOs in metastatic lymph nodes, they appear with less signal reduction, and permit the differentiation of healthy lymph nodes from normal-sized, metastatic nodes.
See also Superparamagnetic Contrast Agents, Superparamagnetic Iron Oxide, Very Small Superparamagnetic Iron Oxide Particles, Blood Pool Agents, Intracellular Contrast Agents.
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Further Reading:
  Basics:
Comparison of Two Superparamagnetic Viral-Sized Iron Oxide Particles Ferumoxides and Ferumoxtran-10 with a Gadolinium Chelate in Imaging Intracranial Tumors
2002   by www.ajnr.org    
  News & More:
Optimized Labelling of Human Monocytes with Iron Oxide MR Contrast Agents
Sunday, 30 November 2003   by rsna2003.rsna.org    
10 SUMMARY AND FUTURE PERSPECTIVES
   by dissertations.ub.rug.nl    
MRI Resources 
Supplies - General - Pacemaker - MRI Centers - Sequences - Case Studies
 
NC100150 InjectionInfoSheet: - Contrast Agents - 
Intro, Overview, 
Characteristics, 
Types of, 
etc.MRI Resource Directory:
 - Contrast Agents -
 
Short name: NC100150, PEG-feron, generic name: Feruglose, preliminary trade name: Clariscan™(1)
NC100150 injection is the code name for an USPIO (ultrasmall superparamagnetic iron oxide) MRI contrast agent under development. Microvessel permeability depends on functional and morphologic characteristics of cancer vessels and on physicochemical properties of the injected contrast medium molecule.
USPIO particles have a favorable pharmacological and tolerance profile and are being tested clinically of the potential for the quantitative characterization of tumor microvasculature and specifically for measures of the microvessel permeability. Iron-based products take advantage of their large molecular size, which prevents diffusion into body tissues. These agents are disposed of by the liver and spleen as particulate matter.
NC100150 Injection (Nycomed Amersham, Amersham Health ) consists of USPIO particles that are composed of single crystals (4- to 7-nm diameter) and stabilized with a carbohydrate polyethylene glycol (PEG) coat. The iron oxide particles have to be suspended in an isotonic glucose solution. The final diameter of an USPIO particle is approximately 20 nm. Blood pool half-life is more than two hours in humans; the particles are taken up by the mononuclear phagocyte system and distributed mainly to the liver and spleen.
NC100150 would compete with the contrast agents Ferumoxytol from AMAG Pharmaceuticals, Inc. and Vasovist™ from EPIX Pharmaceuticals, Inc., but at this time the development of NC100150 Injection is discontinued.


1. IMPORTANT: The trade name Clariscan™ planned to be used at the time of Amersham Health is reused (since 2017) for a contrast agent developed by GE Healthcare. The newly developed Clariscan™ by GE Healthcare is a totally different contrast agent with first approvals in March of 2017. Please read Clariscan™.
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• View the NEWS results for 'NC100150 Injection' (2).Open this link in a new window.
MRI Resources 
MRI Reimbursement - Breast MRI - MRCP - DICOM - Research Labs - Implant and Prosthesis pool
 
Combidex®InfoSheet: - Contrast Agents - 
Intro, Overview, 
Characteristics, 
Types of, 
etc.MRI Resource Directory:
 - Contrast Agents -
 
Combidex® is the brand name (same as Sinerem®) for an ultrasmall superparamagnetic iron oxide (USPIO) in the development pipeline to detect metastatic disease in lymph nodes. Metastatic lymph nodes show less uptake of this MRI contrast agent, which results in less signal decrease and allows the differentiation of normal lymph nodes from normal-sized, metastatic nodes. Combidex® has also potential to be used as a functional molecular imaging agent.
In March 2005, AMAG Pharmaceuticals Inc received an approvable letter from the U.S. Food and Drug Administration with respect to Combidex subject to certain conditions.
See also Ferumoxtran, Drug Development and Approval Process USA, Molecular Imaging and Classifications, Characteristics, etc.

Drug Information and Specification
NAME OF COMPOUND Ferumoxtran, USPIO, AMI-227
DEVELOPER AMAG Pharmaceuticals, Inc.
CENTRAL MOIETY Fe3+/Fe2+
CONTRAST EFFECT T1, predominantly T2
RELAXIVITY r1=25, r2=160, B0=0.47T, r1=23.3, r2=48.9, B0=0.47T
PHARMACOKINETIC Vascular, lymph v. hepatocyte (AG-USPIO)
OSMOLALITY
CONCENTRATION
DOSAGE 2.6 mg Fe/kg
PREPARATION Suspend in an isotonic glucose solution
INDICATION Lymph node, (MR angiography vascular, staging of RES-directed liver diseases)
DEVELOPMENT STAGE
DISTRIBUTOR
PRESENTATION
DO NOT RELY ON THE INFORMATION PROVIDED HERE, THEY ARE NOT A SUBSTITUTE FOR THE ACCOMPANYING PACKAGE INSERT


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• View the DATABASE results for 'Combidex®' (6).Open this link in a new window


• View the NEWS results for 'Combidex®' (1).Open this link in a new window.
 
Further Reading:
  Basics:
The demise of Combidex - Sinerem
Wednesday, 24 March 2010   by www.wellsphere.com    
  News & More:
Combidex, MRI, and identification of nodal metastases
Wednesday, 17 June 2009   by prostatecancerinfolink.net    
Superparamagnetic Iron Oxide–enhanced MR Imaging of Head and Neck Lymph Nodes1
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Contrast AgentsForum -
related threadsInfoSheet: - Contrast Agents - 
Intro, Overview, 
Characteristics, 
Types of, 
etc.MRI Resource Directory:
 - Contrast Agents -
 
Contrast agents are chemical substances introduced to the anatomical or functional region being imaged, to increase the differences between different tissues or between normal and abnormal tissue, by altering the relaxation times. MRI contrast agents are classified by the different changes in relaxation times after their injection.
Positive contrast agents cause a reduction in the T1 relaxation time (increased signal intensity on T1 weighted images). They (appearing bright on MRI) are typically small molecular weight compounds containing as their active element Gadolinium, Manganese, or Iron. All of these elements have unpaired electron spins in their outer shells and long relaxivities.
Some typical contrast agents as gadopentetate dimeglumine, gadoteridol, and gadoterate meglumine are utilized for the central nervous system and the complete body; mangafodipir trisodium is specially used for lesions of the liver and gadodiamide for the central nervous system.
Negative contrast agents (appearing predominantly dark on MRI) are small particulate aggregates often termed superparamagnetic iron oxide (SPIO). These agents produce predominantly spin spin relaxation effects (local field inhomogeneities), which results in shorter T1 and T2 relaxation times.
SPIO's and ultrasmall superparamagnetic iron oxides (USPIO) usually consist of a crystalline iron oxide core containing thousands of iron atoms and a shell of polymer, dextran, polyethyleneglycol, and produce very high T2 relaxivities. USPIOs smaller than 300 nm cause a substantial T1 relaxation. T2 weighted effects are predominant.
A special group of negative contrast agents (appearing dark on MRI) are perfluorocarbons (perfluorochemicals), because their presence excludes the hydrogen atoms responsible for the signal in MR imaging.
The design objectives for the next generation of MR contrast agents will likely focus on prolonging intravascular retention, improving tissue targeting, and accessing new contrast mechanisms. Macromolecular paramagnetic contrast agents are being tested worldwide. Preclinical data shows that these agents demonstrate great promise for improving the quality of MR angiography, and in quantificating capillary permeability and myocardial perfusion.
Ultrasmall superparamagnetic iron oxide (USPIO) particles have been evaluated in multicenter clinical trials for lymph node MR imaging and MR angiography, with the clinical impact under discussion. In addition, a wide variety of vector and carrier molecules, including antibodies, peptides, proteins, polysaccharides, liposomes, and cells have been developed to deliver magnetic labels to specific sites. Technical advances in MR imaging will further increase the efficacy and necessity of tissue-specific MRI contrast agents.
See also Adverse Reaction and Nephrogenic Systemic Fibrosis.

See also the related poll result: 'The development of contrast agents in MRI is'
 
Images, Movies, Sliders:
 Delayed Myocardial Contrast Enhancement from Infarct  Open this link in a new window
      

Courtesy of  Robert R. Edelman
 Left Circumflex Ischemia First-pass Contrast Enhancement  Open this link in a new window
 MR Colonography Gadolinium per Rectum  Open this link in a new window
      

Courtesy of  Robert R. Edelman
 CE MRA of the Aorta  Open this link in a new window
    
SlidersSliders Overview

 
Radiology-tip.comContrast Agents,  Safety of Contrast Agents
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Radiology-tip.comUltrasound Contrast Agents,  Ultrasound Contrast Agent Safety
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• View the DATABASE results for 'Contrast Agents' (122).Open this link in a new window


• View the NEWS results for 'Contrast Agents' (25).Open this link in a new window.
 
Further Reading:
  Basics:
New guidelines urge caution on use of contrast agents during MR scans
Tuesday, 8 August 2017   by www.dotmed.com    
Manganese-based MRI contrast agents: past, present and future
Friday, 4 November 2011   by www.ncbi.nlm.nih.gov    
A safer approach for diagnostic medical imaging
Monday, 29 September 2014   by www.eurekalert.org    
Drastic market changes with MRI contrast media and PET radiopharmaceuticals emerging as most promising segments
Thursday, 21 October 2004   by www.news-medical.net    
  News & More:
Sodium MRI May Show Biomarker for Migraine
Friday, 1 December 2017   by psychcentral.com    
Manganese-based MRI contrast agent may be safer alternative to gadolinium-based agents
Wednesday, 15 November 2017   by www.eurekalert.org    
3D 'bone maps' could spot early signs of osteoporosis
Monday, 27 February 2017   by www.gmanetwork.com    
New Study Sheds Light on Safety of Gadolinium-Based Contrast Agents
Wednesday, 29 November 2017   by www.empr.com    
Engineered atherosclerosis-specific zinc ferrite nanocomplex-based MRI contrast agents
Monday, 18 January 2016   by 7thspace.com    
A natural boost for MRI scans
Monday, 21 October 2013   by www.eurekalert.org    
For MRI, time is of the essence A new generation of contrast agents could make for faster and more accurate imaging
Tuesday, 28 June 2011   by scienceline.org    
MRI Resources 
Hospitals - Open Directory Project - Pathology - MRI Technician and Technologist Schools - Chemistry - Contrast Enhanced MRI
 
Sinerem®InfoSheet: - Contrast Agents - 
Intro, Overview, 
Characteristics, 
Types of, 
etc.MRI Resource Directory:
 - Contrast Agents -
 
Sinerem® is the brand name (same as Combidex®) for an ultrasmall superparamagnetic iron oxide (USPIO) to detect metastatic disease in lymph nodes. Metastatic nodes show less uptake of this MRI contrast agent, which results in less signal decrease and allows the differentiation of normal lymph nodes from normal-sized, metastatic nodes.
Lymph node imaging with Sinerem® is performed 24 to 36 hours after slow infusion. Normal lymph nodes turn black post contrast, namely on T2* weighted images. Metastatic lymph nodes remain unchanged in signal intensity.
Indication and Diseases: Cancer, Imaging for diagnosis, Lymphatic disorders.
See Ferumoxtran, and Classifications, Characteristics, etc.

Guerbet decided in 2007 to withdraw its Marketing Authorisation Application (MAA) for Sinerem.


Drug Information and Specification
NAME OF COMPOUND Ferumoxtran, USPIO, AMI-227
DEVELOPER AMAG Pharmaceuticals, Inc.
CENTRAL MOIETY Fe3+/Fe2+
CONTRAST EFFECT T1, T2
RELAXIVITY r1=25, r2=160, B0=0.47T, r1=23.3, r2=48.9, B0=0.47T
PHARMACOKINETIC Vascular, lymph v. hepatocyte (AG-USPIO)
OSMOLALITY
CONCENTRATION
DOSAGE 2.6 mg Fe/kg
PREPARATION Suspend in an isotonic glucose solution
INDICATION MR angiography vascular, staging of RES-directed liver diseases, lymph nodes
DEVELOPMENT STAGE -
DISTRIBUTOR
PRESENTATION
DO NOT RELY ON THE INFORMATION PROVIDED HERE, THEY ARE NOT A SUBSTITUTE FOR THE ACCOMPANYING PACKAGE INSERT
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• View the DATABASE results for 'Sinerem®' (6).Open this link in a new window

 
Further Reading:
  Basics:
The demise of Combidex - Sinerem
Wednesday, 24 March 2010   by www.wellsphere.com    
  News & More:
Ultrasmall Superparamagnetic Particles of Iron Oxide-enhanced in vivo MRI of human atherosclerotic plaques.(.pdf)
MRI Resources 
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