Gadolinium

Introduction

Gadolinium (Gd) is a chemical element with an atomic number of 64 in the periodic table of elements. There’s about 6.2 mg/kg of this soft metal occurring in Earth’s crust. This makes gadolinium one of the most abundant rare-earth elements found in nature.

Being a member of the lanthanides family of periodic table elements, gadolinium is a divalent element with strong conductive and ferromagnetic properties. 

Fact Box

Chemical and Physical Properties of Gadolinium

The symbol in the periodic table of elements: Gd

Atomic number: 64

Atomic weight (mass): 157.25 g.mol-1

Group number: 19 (Lanthanides)

Period: 6

Color: A silvery-white lustrous metal

Physical state: Solid at room temperature

Half-life: From 0.4 s to 1.08×1014 years

Electronegativity according to Pauling: 1.1 

Density: 7.9 g.cm-3 at 20°C

Melting point: 1313°C, 2395°F, 1586 K

Boiling point: 3273°C, 5923°F, 3546 K

Van der Waals radius: 273 pm

Ionic radius: 2.54 

Isotopes: 17

Most characteristic isotope:158Gd

Electronic shell: [Xe] 4f75d16s2

The energy of the first ionization: 591.4 kJ.mol-1

The energy of the second ionization: 1165.5 kJ.mol-1

Discovery date: In 1880 by Charles Galissard de Marignac

 

With the periodic table symbol (Gd), atomic number 64, atomic mass of 157.25 g.mol-1, and electron configuration [Xe] 4f75d16s2, gadolinium is a soft and slightly malleable silvery-white metal that reaches its boiling point at 3273°C (5923°F, 3546 K), while the melting point is achieved at 1313°C (2395°F, 1586 K). 

 

This member of the lanthanide family of elements has oxidation states of 1, 2, and 3, as well as an electronegativity of 1.1 according to Pauling. It’s an excellent conductor of heat and electricity and possesses strong ferromagnetic properties when exposed to a temperature below its Curie point of 20 °C (68 °F). 

 

Furthermore, gadolinium crystallizes in a hexagonal, close-packed alpha form at room temperature. Upon exposure to a temperature of 1235°C, this rare-earth metal adopts the body-centered cubic beta form. Being relatively stable in dry air, gadolinium metal tarnishes when it comes into contact with humid air and is soluble by diluted acid. As a strong reducing agent, gadolinium reduces oxides of several metals into their elements. 

How Was Gadolinium Discovered?

 

The path of gadolinium’s discovery begins in 1880, in a laboratory in Geneva, Switzerland. That year, the Swiss chemist Charles Galissard de Marignac (1817 – 1894) decided to clarify his suspicion on the prior results obtained by Carl Mosander.

Namely, he was convinced that what Mosander thought was a new element labeled as didymium, was in fact a chemical compound. His scientific doubts were reinforced by the results obtained by the French chemists Marc Delafontaine and Paul-Émile Lecoq de Boisbaudran. 

 

 

Two years earlier, these two scientists had successfully separated samarium from didymium, extracted from the mineral samarskite. Delafontaine and de Boisbaudran attempted spectroscopy on the sample found in the Urals. Their experiment uncovered the most vital information – the spectral lines of the analyzed sample were unlike the source they were produced from. 

 

 

Based upon the scientific results obtained by his French colleagues, as well as upon his personal analysis, de Marignac managed to confirm that the previously unknown spectroscopic lines in an oxide preparation taken from the mineral samarskite were a property of the new chemical element – gadolinium.

 

 

In 1935, the French chemist and engineer Felix Trombe (1906–1985) succeeded in isolating the pure form of gadolinium for the first time. 

How Did Gadolinium Get Its Name?

This lanthanide got its name after the mineral ore in which it occurs, the gadolinite. Moreover, the mineral gadolinite was named after the Finnish chemist, physicist, and mineralogist Johan Gadolin (1760 – 1852) – the founder of Finnish chemistry research, as well as a distinguished member of the Royal Swedish Academy of Sciences. Gadolin was also one of the first chemists who provided practical experience to his students by allowing them to use his laboratory.

Where Can You Find Gadolinium?

The minerals monazite and bastnasite are the main natural sources of gadolinium. The chemical processes involving ion-exchange and the solvent extraction techniques make this rare-earth metal even more commercially available today. Most often, the synthetically produced gadolinium is made by reduction of the anhydrous fluoride with metallic calcium.

 

Gadolinium Use in Everyday Life

This chemical is not commonly used in everyday life. However, it has several specialized applications, among which we can list the following:

 

  • Gadolinium is applied in the process of making phosphors for color TV tubes;
  • It’s used as a nuclear control rod material and in nuclear marine propulsion systems;
  • This chemical element also finds application in making gadolinium yttrium garnets;
  • When added to iron and chromium alloys, even the smallest quantity of gadolinium can make them more easily workable and resistant to both high temperatures and oxidation;
  • Gadolinium compounds are applied in magnetic resonance imaging (MRI), a technique used in cancerous tumor diagnostics. 

The Use of Gadolinium in Magnetic Resonance Imaging

MRI or magnetic resonance imaging is a non-invasive diagnostic technique in radiology aimed at the early discovery of cancerous tumors and other diseases, as well as monitoring their progress. By applying MRI contrast agents, the magnetic resonance technique is able to provide anatomical images of the body’s soft tissues and organs, as well as of the physiological processes of the body. The MRI images are created with the help of a magnetic field, radio waves, and a specialized computer. 

 

This technique used in radiology can detect:


  • Traumatic brain injuries;
  • Aneurysms;
  • Blockages of the blood vessels;
  • Developmental anomalies;
  • Herniated discs;
  • Pinched nerves;
  • Multiple sclerosis;
  • Signs of stroke;
  • Carotid artery disease;
  • Disc herniations;
  • Arteriovenous malformations;
  • Spinal cord compression;
  • Dementia causes;
  • Cartilage and bone structure injuries;
  • Various infections;
  • Causes of headache brain tumors.

 

Gadolinium-based contrast agents (GBCAs) are used in the process of the MRI scan in order to improve the visibility of the internal structures of the body which are subject to medical diagnostics. 

 

Namely, in order for the image of the internal structure of the body to be registered by the magnetic field and the computer, contrast media composed of gadolinium(III) is injected into the bloodstream. After the MRI procedure, this heavy metal is eliminated from the body via the kidneys. However, renal insufficiency patients are unable to eliminate gadolinium from their body, which increases the risk of adverse effects. 

Why Is Gadolinium Used As an MRI Contrasting Agent?

This chemical element is used as an MRI agent due to its strong ferromagnetic properties. When gadolinium becomes absorbed by the targeted tissues via the bloodstream, it alters the magnetic properties of water molecules. In this way, the gadolinium-targeted tissues become clearly visible to the MRI scanner which in that way can detect all abnormalities and dysfunctionalities. 

 

In a way, gadolinium ‘marks’ the soft tissues for better visibility by the computer. Typically, gadolinium-based contrast agents are applied in MR angiogram (MRA) diagnostics for more thorough medical analysis of the arteries and veins. 

Types of Gadolinium Contrast Agents

Based upon the shape of the organic ligand, gadolinium agents for MRI contrasting fall into two broad categories: 

 

  • Linear contrast agents (gadopentetate dimeglumine, gadobenate dimeglumine, gadodiamide, and gadoversetamide);
  • Macrocyclic contrast agents that contain organic rings complexed with Gd3+ (gadoterate meglumine, gadobutrol, and gadoteridol). 

 

According to the bodily area targeted by the MRI diagnostic scan examination, the gadolinium contrast agents can be classified into several categories:

 

  • Extracellular fluid agents;
  • Blood pool agents;
  • Hepatobiliary (liver) agents;
  • Agents approved for human use.

Extracellular Fluid Agents

This list of gadolinium contrast agents comprises:


  • Gadoterate (Dotarem, Clariscan);
  • Gadodiamide (Omniscan);
  • Gadobenate (MultiHance);
  • Gadopentetate (Magnevist);
  • Gadoteridol (ProHance);
  • Gadoversetamide (OptiMARK);
  • Gadobutrol (Gadovist [EU] / Gadavist [US]);
  • Gadopentetic acid dimeglumine (Magnetol).

Blood Pool Agents

The category of blood pool agents lists the following MRI contrast agents:

 

  • Gadofosveset (Ablavar, formerly Vasovist);
  • Gadocoletic acid;
  • Gadomelitol;
  • Gadomer 17.

Hepatobiliary (Liver) Agents

  • Gadoxetic acid (Primovist [EU] / Eovist [US])

Agents Approved For Human Use

 

The following list of intravenous drugs consists of gadolinium chelated contrast agents that have been approved for human use by the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA):

 

  • EMA FDA Gadoterate (Dotarem; European: Clariscan);
  • EMA FDA Gadodiamide (Omniscan);
  • EMA FDA Gadobenate (MultiHance);
  • EMA FDA Gadopentetate (Magnevist; European: Magnegita, Gado-MRT ratiopharm);
  • EMA FDA Gadoteridol (ProHance);
  • FDA Gadofosveset (Ablavar, formerly Vasovist);
  • EMA FDA Gadoversetamide (OptiMARK);
  • EMA FDA Gadoxetate (Eovist; European: Primovist);
  • EMA FDA Gadobutrol (Gadovist).

Adverse Reactions to Gadolinium Contrast Agents

The paramagnetic properties of ionized gadolinium certainly contribute immensely to the advance of computer diagnostics. Gadolinium-based contrast agents have been compounded with organic chelating agents in order to reduce the toxicity risks from the unbound gadolinium ions while maintaining their contrast properties. 

 

However, in some cases, certain complications may occur as an adverse reaction of the body to the gadolinium contrast agents. Even though the gadolinium contrast agents are eliminated from the body via the kidneys after MRI diagnostics, in some patients, the GCAs can trigger the occurrence of nephrogenic systemic fibrosis or gadolinium retention.

Nephrogenic Systemic Fibrosis

Nephrogenic systemic fibrosis or nephrogenic fibrosing dermopathy (NFD) is a progressive multiorgan system fibrosing disease that occurs predominantly in patients with impaired renal function or perioperative liver transplantation. It characterizes severe skin tightening of the affected individual.

These patients are at a greater risk of developing nephrogenic systemic fibrosis after being injected with gadolinium-based contrast agents for the purpose of the MRI scan diagnostics. 

 

Since the reasons behind the connection between gadolinium and impaired renal function are not yet clarified by medical researchers, the mortality percentage of this progressive disease is relatively high. 

Gadolinium Retention 

In most cases, gadolinium that was injected as a contrasting agent for an MRI is eliminated from the body via urine within 24 hours, However, in cases of acute renal failure or severe chronic kidney disease gadolinium retention may occur. 

 

 

That’s why radiologists perform screening for chronic kidney disease of all patients prior to their MRI scan diagnostics enhanced with gadolinium-based contrast agents. It’s not rare for this paramagnetic substance to be retained in a patient’s body for several months or even years after the performed MRI scan. This, in turn, may lead to severe side effects resulting in more serious medical conditions. 

 

The patients with gadolinium retention may experience the following symptoms after being injected with linear GBCAs:


  • Vertigo;
  • Brain fog;
  • Headache;
  • Difficulty breathing;
  • Pain in the bones or joints;
  • Vision or hearing changes;
  • Nausea, vomiting, or diarrhea;
  • Burning or prickling skin sensations;
  • Thickening or discoloration of the skin;
  • Irregular heartbeat;
  • Mild to severe allergic reactions.

 

 

If the aforementioned symptoms persist for a longer time, gadolinium deposition disease may develop. For more information on gadolinium retention, please visit: https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-warns-gadolinium-based-contrast-agents-gbcas-are-retained-body

Gadolinium Deposition Disease

 

Despite the beneficial effect of GBCAs, this medical imaging enhancer still leaves behind some gadolinium deposits. They accumulate mainly in the kidneys, brain, and bones, even in patients who don’t suffer from renal failure and have normal kidney function. 

 

According to a study published by the Journal of the American College of Radiology, these macrocyclic GBCA materials tend to accumulate in the dentate nuclei and globus pallidus of the brain, thus developing a high signal intensity among the neuron cells of the brain.

This is especially true for the linear agents, such as gadopentetate, gadobenate, gadodiamide, and gadoxetate. The results of this study further confirm that deposition of these linear agents may occur even in patients with normal renal function upon exposure to gadolinium chelates. 

What Are the Symptoms of Gadolinium Deposition Disease?

The symptoms reported in patients affected by the gadolinium deposition disease include:

 

  • Stiffness of the joints;
  • Cramping of muscles;
  • Tiredness;
  • Buzzing sensation in the ears;
  • Vertigo;
  • Cognitive problems;
  • Skin changes (discoloration, pain, and thickening);
  • Peripheral neuropathic pain localized in either a hand or a foot. 

How Dangerous Is Gadolinium?

The pure, elemental form of gadolinium is a highly toxic substance. In order to be safe for use in the human body as a gadolinium-based contrast agent (GBCA), Gd undergoes the process of chelation. GBCAs are considered to be safer than the iodinated contrast agents that are used in X-ray radiography or computed tomography. 

Gadolinium Toxicity

The free, elemental form of gadolinium, as well as its compounds, are considered to be moderately toxic. Although very few people may come into contact with this rare-earth heavy metal in the living environment, gadolinium has a significant role in medicine and the diagnostics of some of the most complex medical conditions. 

 

Gadolinium toxicity may lead to adverse health effects upon its accumulation in the body. Since compounds of this moderately toxic element must be injected into the body when conducting MRIs, gadolinium is priorly chelated, since in this way it adopts a non-toxic form with a very short half-life in the body.

Environmental Effects of Gadolinium

The MRI imaging machines containing the toxic rare earth element gadolinium are considered as the only threat to the environment due to the high exposure to gadolinium. Namely, during the process of the manufacturing of this life saving medical technology, the wastewaters of the plants end up directly in the environment, thus contaminating the soil and the surface waters to a lesser extent. 

Isotopes of Gadolinium

There are seventeen isolated forms of gadolinium among which seven stable isotopes of gadolinium compose the elemental form of this lanthanide element (154Gd, 155Gd, 156Gd, 157Gd, 158Gd, and 160Gd). The isotopes 152Gd and 158Gd are the most abundant gadolinium forms that occur in nature, while the naturally occurring gadolinium-152 isotope has the longest half-life of 1.08×1014 years. 

 

A total of ten metastable isomers of the gadolinium isotopes have been detected. The most stable gadolinium isomer is 143mGd (t1/2 = 110 seconds), followed by 145mGd (t1/2 = 85 seconds), and 141mGd (t1/2 = 24.5 seconds).

 

Gadolinium also has thirty radioactive isotopes, with an average half-life of less than 24.6 seconds. 

 

Nuclide

[n 1]

Z N Isotopic mass (Da)

[n 2][n 3]

Half-life

[n 4][n 5]

Decay

mode

[n 6]

Daughter

isotope

[n 7][n 8]

Spin and

parity

[n 9][n 5]

Natural abundance (mole fraction)
Excitation energy[n 5] Normal proportion Range of variation
134Gd 64 70 133.95537(43)# 0.4# s 0+
135Gd 64 71 134.95257(54)# 1.1(2) s 3/2−
136Gd 64 72 135.94734(43)# 1# s [>200 ns] β+ 136Eu
137Gd 64 73 136.94502(43)# 2.2(2) s β+ 137Eu 7/2+#
β+, p (rare) 136Sm
138Gd 64 74 137.94012(21)# 4.7(9) s β+ 138Eu 0+
139Gd 64 75 138.93824(21)# 5.7(3) s β+ 139Eu 9/2−#
Β+, p (rare) 138Sm
140Gd 64 76 139.93367(3) 15.8(4) s β+ 140Eu 0+
141Gd 64 77 140.932126(21) 14(4) s β+ (99.97%) 141Eu (1/2+)
β+, p (.03%) 140Sm
142Gd 64 78 141.92812(3) 70.2(6) s β+ 142Eu 0+
143Gd 64 79 142.92675(22) 39(2) s β+ 143Eu (1/2)+
β+, α (rare) 139Pm
β+, p (rare) 142Sm
144Gd 64 80 143.92296(3) 4.47(6) min β+ 144Eu 0+
145Gd 64 81 144.921709(20) 23.0(4) min β+ 145Eu 1/2+
146Gd 64 82 145.918311(5) 48.27(10) d EC 146Eu 0+
147Gd 64 83 146.919094(3) 38.06(12) h β+ 147Eu 7/2−
148Gd 64 84 147.918115(3) 74.6(30) y α 144Sm 0+
β+β+ (rare) 148Sm
149Gd 64 85 148.919341(4) 9.28(10) d β+ 149Eu 7/2−
α (4.34×10−4%) 145Sm
150Gd 64 86 149.918659(7) 1.79(8)×106 y α 146Sm 0+
β+β+ (rare) 150Sm
151Gd 64 87 150.920348(4) 124(1) d EC 151Eu 7/2−
α (10−6%) 147Sm
152Gd[n 10] 64 88 151.9197910(27) 1.08(8)×1014 y α 148Sm 0+ 0.0020(1)
153Gd 64 89 152.9217495(27) 240.4(10) d EC 153Eu 3/2−
154Gd 64 90 153.9208656(27) Observationally Stable[n 11] 0+ 0.0218(3)
155Gd[n 12] 64 91 154.9226220(27) Observationally Stable[n 13] 3/2− 0.1480(12)
156Gd[n 12] 64 92 155.9221227(27) Stable 0+ 0.2047(9)
157Gd[n 12] 64 93 156.9239601(27) Stable 3/2− 0.1565(2)
158Gd[n 12] 64 94 157.9241039(27) Stable 0+ 0.2484(7)
159Gd[n 12] 64 95 158.9263887(27) 18.479(4) h β 159Tb 3/2−
160Gd[n 12] 64 96 159.9270541(27) Observationally Stable[n 14] 0+ 0.2186(19)
161Gd 64 97 160.9296692(29) 3.646(3) min β 161Tb 5/2−
162Gd 64 98 161.930985(5) 8.4(2) min β 162Tb 0+
163Gd 64 99 162.93399(32)# 68(3) s β 163Tb 7/2+#
164Gd 64 100 163.93586(43)# 45(3) s β 164Tb 0+
165Gd 64 101 164.93938(54)# 10.3(16) s β 165Tb 1/2−#
166Gd 64 102 165.94160(64)# 4.8(10) s β 166Tb 0+
167Gd 64 103 166.94557(64)# 3# s β 167Tb 5/2−#
168Gd 64 104 167.94836(75)# 300# ms β 168Tb 0+
169Gd 64 105 168.95287(86)# 1# s β 169Tb 7/2−#

Source: Wikipedia

List of Gadolinium Compounds 

In most of its compounds, gadolinium adopts a trivalent state (Gd3+). This chemical element most often forms chlorides, nitrates, oxides, iodides, and nitrides:


  • Gadolinium trifluoride GdF3
  • Gadolinium trichloride GdCl3
  • Gadolinium tribromide GdBr3
  • Gadolinium diiodide GdI2
  • Gadolinium triiodide GdI3
  • Digadolinium trioxide: Gd2O3
  • Gadolinium selenide: GdSe
  • Di-gadolinium tri-telluride: Gd2Te3
  • Gadolinium nitride GdN
  • Gadolinium trichloride hexahydrate: GdCl3.6H2O

Organo-Gadolinium Compounds

    • Gadobenic acid – It’s used as a gadolinium-based MRI contrast medium in the form of methylglucamine salt meglumine gadobenate (INNm) or gadobenate dimeglumine (USAN). 
    • Gadobutrol A gadolinium-based MRI contrast agent (GBCA) sold on the pharmaceutical market by Bayer AG as Gadovist, and by Bayer HealthCare Pharmaceuticals as Gadavist. It’s used in diagnostic magnetic resonance imaging (MRI), as well as in contrast-enhanced magnetic resonance angiography (CE-MRA). 
    • Gadodiamide – This gadolinium-based MRI contrast agent is applied in MR imaging diagnostics of the blood vessels; its common name on the pharmaceutical market is Omniscan. Gadodiamide is predominantly used for cranial and spinal magnetic resonance imaging (MRI). Being highly toxic, this gadolinium compound is often related to the occurrence of nephrogenic systemic fibrosis (NSF) in patients suffering from dysfunctional kidneys. It also tends to accumulate in the brain’s tissue. 
    • Gadofosveset – This gadolinium-based MRI contrast agent can be found under the trade names Vasovist or Ablavar. By binding itself to the human serum albumin, gadofosveset performs the function of a blood pool agent. 
    • Gadolinium acetylacetonate – Being a gadolinium complex of acetylacetone, gadolinium acetylacetonate is applied as precursors in the making of gadolinia-doped ceria (GDC) gel powders.
    • Gadopentetic acid – With the chemical formula A2[Gd(DTPA)(H2O)], this gadolinium-based MRI contrast agent was the first MRI contrast agent in 1987 introduced in radiology by the research-centered German multinational pharmaceutical company, Schering AG. The clinical use of the gadopentetic acid targets the most sensitive imaging procedures, offering a better image of the intracranial lesions, abnormal vascular changes in the blood-supplying system of the brain, as well as of inflamed or diseased tissues. This GBCA also may trigger the toxic reaction labeled as nephrogenic systemic fibrosis.
    • Gadoteric acid – Gadoterate meglumine, or the gadoteric acid marketed under the names Artirem, Dotarem, and Clariscan, is another type of gadolinium-based MRI contrast agent with the molecular structure of a macrocycle. Due to its strong magnetic properties, the gadoteric acid increases the brightness of the MR images when exposed to a magnetic field. Administered through an intravenous bolus injection, this GBCA is suitable for younger patients. 
    • Gadoteridol Found on the pharmaceutical market under the brand-name ProHance, this type of gadolinium-based MRI contrast agent finds its application in the magnetic resonance imaging of the central nervous system. 
    • Gadoversetamide Labeled with the trade-name OptiMARK, the gadoversetamide is a gadolinium-based MRI contrast agent typically used in the magnet scans of the brain, spine, and liver.
    • Motexafin gadolinium – This inhibitor of thioredoxin reductase and ribonucleotide reductase is considered to be an adequate chemotherapeutic agent administered in the treatment of brain cancer metastases.

5 Interesting Facts and Explanations

  1. Gadolinium’s attraction to a magnetic field is stronger than the one of nickel.
  2. Only the oxidized form of gadolinium can be found in nature. 
  3. With 49,000 barns, gadolinium is the chemical element with the highest thermal neutron capture cross-section of any other known substance.  
  4. The discovery of samarium in 1853 and ytterbium in 1878 are among the many great achievements of the Swiss chemist Jean Charles Galissard de Marignac. 
  5. This member of the lanthanide family is the only heavy metal that is suitable for MRI enhancement.