Gadodiamide
Encyclopedia
Gadodiamide is a gadolinium-based MRI contrast agent, used in MR
imaging procedures to assist in the visualization of blood vessels. It is commonly marketed under the trade name
Omniscan.
for cranial and spinal magnetic resonance imaging
(MRI) and for general MRI of the body after intravenous administration.
The product provides contrast enhancement and facilitates visualisation of abnormal structures or lesions in various parts of the body including the central nervous system (CNS
). It does not cross an intact blood brain barrier but might give enhancement in pathological conditions.
(NSF) in some patients with severe kidney
problems.
Some articles suggested that over 60 persons examined with Omniscan had either died or had been severely disabled as a result of the use of the product. However, a recent report by the Danish Medicines Agency
stated that there were 35 cases of NSF reported after use of Omniscan and that 33 of these had been reported from a single centre in Copenhagen
.
However, already in 2001, a case of renal toxicity and pancreatitis
associated with Omniscan use for arteriography had been reported. In their paper, the authors also referred to two other previous case reports (1998 and 1999) of acute renal failure after gadoteridol
(Prohance) intraarterially and acute pancreatitis after intravenous gadolinium-DTPA A case of cardiac arrest
has also been reported. Gadopentetate dimeglumine (Magnevist) was administered during an MR study of the head, and from the rapid onset of signs and symptoms and subsequent cardiovascular arrest, a cause-and-effect relationship was suggested.
In the interest of public health, it seems important that not only renal disease should be considered a factor when decisions about the use of this kind of MRI contrast is taken.
Release of Gd3+ from the complex is said to be responsible for the toxicity associated with gadolinium
complexes; this release appears to be a consequence of Zn2+
, Cu2+
, and Ca2+
transmetallation in vivo. This hypothesis is supported by 1) acute toxicity experiments, which demonstrate that despite a 50-fold range of LD50 values for four Gd complexes, all become lethally toxic when they release precisely the same quantity of Gd3+, and 2) by subchronic rodent toxicity experiments, which demonstrate a set of gross and microscopic findings similar to those known to be caused by Zn2+ deficiency. A recent review takes the question of toxicity caused by loss of gadolinium from the complex. "The challenge for nephrologists includes (a) evidence of transmetallation, such as gadolinium deposits in bone
, increased urinary zinc excretion, iron-transferrin dissociation or 'spurious hypocalcemia' in exposed people"
Nephrogenic systemic fibrosis (NSF) is a rare, but potentially serious, acquired systemic disease. To date, it has only been reported in patients with either severe, end-stage or acute
renal impairment. There have been no reports of NSF associated with gadolinium-based contrast agents (GBCA) in those patients with mild or moderate renal impairment or with normal kidney function. This latter group of patients make up the significant majority of the population who undergo imaging procedures. To date, over 120 million doses of GBCA have been given over a 20-year period. Of those, more than 40 million doses were Omniscan.
One of the many, as yet unanswered, questions regarding NSF is why certain centers have relatively high numbers of NSF reports whereas the majority of hospitals using gadolinium contrast agents have no reports.
Magnetic resonance
Magnetic resonance can mean:*Nuclear magnetic resonance*Electron spin resonance*Magnetic resonance imaging *Functional magnetic resonance imaging *Muon spin spectroscopy...
imaging procedures to assist in the visualization of blood vessels. It is commonly marketed under the trade name
Trade name
A trade name, also known as a trading name or a business name, is the name which a business trades under for commercial purposes, although its registered, legal name, used for contracts and other formal situations, may be another....
Omniscan.
Uses
Gadodiamide is a contrast mediumContrast medium
A medical contrast medium is a substance used to enhance the contrast of structures or fluids within the body in medical imaging...
for cranial and spinal magnetic resonance imaging
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
(MRI) and for general MRI of the body after intravenous administration.
The product provides contrast enhancement and facilitates visualisation of abnormal structures or lesions in various parts of the body including the central nervous system (CNS
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
). It does not cross an intact blood brain barrier but might give enhancement in pathological conditions.
Media coverage
In February 2008, Danish media stated that gadolinium-based agents may be associated with a toxic reaction known as nephrogenic systemic fibrosisNephrogenic systemic fibrosis
Nephrogenic systemic fibrosis or nephrogenic fibrosing dermopathy is a rare and serious syndrome that involves fibrosis of skin, joints, eyes, and internal organs. Its cause is not fully understood...
(NSF) in some patients with severe kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
problems.
Some articles suggested that over 60 persons examined with Omniscan had either died or had been severely disabled as a result of the use of the product. However, a recent report by the Danish Medicines Agency
Danish Medicines Agency
The Danish Medicines Agency is an agency under the Danish Ministry of Health and Prevention.The purpose of the agency is to ensure that medicinal products used in Denmark are of satisfactory quality, are safe to use and that they have the desired effect...
stated that there were 35 cases of NSF reported after use of Omniscan and that 33 of these had been reported from a single centre in Copenhagen
Copenhagen
Copenhagen is the capital and largest city of Denmark, with an urban population of 1,199,224 and a metropolitan population of 1,930,260 . With the completion of the transnational Øresund Bridge in 2000, Copenhagen has become the centre of the increasingly integrating Øresund Region...
.
However, already in 2001, a case of renal toxicity and pancreatitis
Pancreatitis
Pancreatitis is inflammation of the pancreas. It occurs when pancreatic enzymes that digest food are activated in the pancreas instead of the small intestine. It may be acute – beginning suddenly and lasting a few days, or chronic – occurring over many years...
associated with Omniscan use for arteriography had been reported. In their paper, the authors also referred to two other previous case reports (1998 and 1999) of acute renal failure after gadoteridol
Gadoteridol
Gadoteridol is a gadolinium-based MRI contrast agent, used particularly in the imaging of the central nervous system. It is sold under the brand name ProHance....
(Prohance) intraarterially and acute pancreatitis after intravenous gadolinium-DTPA A case of cardiac arrest
Cardiac arrest
Cardiac arrest, is the cessation of normal circulation of the blood due to failure of the heart to contract effectively...
has also been reported. Gadopentetate dimeglumine (Magnevist) was administered during an MR study of the head, and from the rapid onset of signs and symptoms and subsequent cardiovascular arrest, a cause-and-effect relationship was suggested.
In the interest of public health, it seems important that not only renal disease should be considered a factor when decisions about the use of this kind of MRI contrast is taken.
Release of Gd3+ from the complex is said to be responsible for the toxicity associated with gadolinium
Gadolinium
Gadolinium is a chemical element with the symbol Gd and atomic number 64. It is a silvery-white, malleable and ductile rare-earth metal. It is found in nature only in combined form. Gadolinium was first detected spectroscopically in 1880 by de Marignac who separated its oxide and is credited with...
complexes; this release appears to be a consequence of Zn2+
Zinc
Zinc , or spelter , is a metallic chemical element; it has the symbol Zn and atomic number 30. It is the first element in group 12 of the periodic table. Zinc is, in some respects, chemically similar to magnesium, because its ion is of similar size and its only common oxidation state is +2...
, Cu2+
Copper
Copper is a chemical element with the symbol Cu and atomic number 29. It is a ductile metal with very high thermal and electrical conductivity. Pure copper is soft and malleable; an exposed surface has a reddish-orange tarnish...
, and Ca2+
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
transmetallation in vivo. This hypothesis is supported by 1) acute toxicity experiments, which demonstrate that despite a 50-fold range of LD50 values for four Gd complexes, all become lethally toxic when they release precisely the same quantity of Gd3+, and 2) by subchronic rodent toxicity experiments, which demonstrate a set of gross and microscopic findings similar to those known to be caused by Zn2+ deficiency. A recent review takes the question of toxicity caused by loss of gadolinium from the complex. "The challenge for nephrologists includes (a) evidence of transmetallation, such as gadolinium deposits in bone
Bone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
, increased urinary zinc excretion, iron-transferrin dissociation or 'spurious hypocalcemia' in exposed people"
Nephrogenic systemic fibrosis (NSF) is a rare, but potentially serious, acquired systemic disease. To date, it has only been reported in patients with either severe, end-stage or acute
Acute (medicine)
In medicine, an acute disease is a disease with either or both of:# a rapid onset, as in acute infection# a short course ....
renal impairment. There have been no reports of NSF associated with gadolinium-based contrast agents (GBCA) in those patients with mild or moderate renal impairment or with normal kidney function. This latter group of patients make up the significant majority of the population who undergo imaging procedures. To date, over 120 million doses of GBCA have been given over a 20-year period. Of those, more than 40 million doses were Omniscan.
One of the many, as yet unanswered, questions regarding NSF is why certain centers have relatively high numbers of NSF reports whereas the majority of hospitals using gadolinium contrast agents have no reports.