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Thursday, May 16, 2019

Technetium-99m

From Wikipedia, the free encyclopedia

Technetium-99m,  99mTc
First technetium-99m generator - 1958.jpg
The first technetium-99m generator, 1958.
A Tc-99m pertechnetate solution is
being eluted from Mo-99 molybdate
bound to a chromatographic substrate
General
Name, symbolTechnetium-99m,99mTc
Neutrons56
Protons43
Nuclide data
Half-life6.0067 hours
Parent isotopes99Mo (65.976 h)
Decay products99Tc
Isotope mass98.9063 u
Spin1/2-
Excess energy-87327.195 keV
Binding energy8613.603 keV
Decay modes
Decay modeDecay energy (MeV)
Isomeric transition
γ emission 87.87%
98.6%: 0.1405 MeV
1.4%: 0.1426

A technetium injection contained in a shielded syringe
 
Technetium-99m is a metastable nuclear isomer of technetium-99 (itself an isotope of technetium), symbolized as 99mTc, that is used in tens of millions of medical diagnostic procedures annually, making it the most commonly used medical radioisotope.

Technetium-99m is used as a radioactive tracer and can be detected in the body by medical equipment (gamma cameras). It is well suited to the role, because it emits readily detectable gamma rays with a photon energy of 140 keV (these 8.8 pm photons are about the same wavelength as emitted by conventional X-ray diagnostic equipment) and its half-life for gamma emission is 6.0058 hours (meaning 93.7% of it decays to 99Tc in 24 hours). The relatively "short" physical half-life of the isotope and its biological half-life of 1 day (in terms of human activity and metabolism) allows for scanning procedures which collect data rapidly but keep total patient radiation exposure low. The same characteristics make the isotope suitable only for diagnostic but never therapeutic use.

Technetium-99m was discovered as a product of cyclotron bombardment of molybdenum. This procedure produced molybdenum-99, a radionuclide with a longer half-life (2.75 days), which decays to Tc-99m. At present, molybdenum-99 (Mo-99) is used commercially as the easily transportable source of medically used Tc-99m. In turn, this Mo-99 is usually created commercially by fission of highly enriched uranium in aging research and material testing nuclear reactors in several countries.

History

Discovery

In 1938, Emilio Segrè and Glenn T. Seaborg isolated for the first time the metastable isotope technetium-99m, after bombarding natural molybdenum with 8 MeV deuterons in the 37-inch (940 mm) cyclotron of Ernest Orlando Lawrence's Radiation laboratory. In 1970 Seaborg explained that
we discovered an isotope of great scientific interest, because it decayed by means of an isomeric transition with emission of a line spectrum of electrons coming from an almost completely internally converted gamma ray transition. [actually, only 12% of the decays are by internal conversion] (...) This was a form of radioactive decay which had never been observed before this time. Segrè and I were able to show that this radioactive isotope of the element with the atomic number 43 decayed with a half-life of 6.6 h [later updated to 6.0 h] and that it was the daughter of a 67-h [later updated to 66 h] molybdenum parent radioactivity. This chain of decay was later shown to have the mass number 99, and (...) the 6.6-h activity acquired the designation ‘technetium-99m.
Later in 1940, Emilio Segrè and Chien-Shiung Wu published the experimental results of the analysis of fission products of uranium-235, among which was present molybdenum-99, and detected the 6-h activity of element 43, later labelled as technetium-99m.

Early medical applications in the United States

Tc-99m remained a scientific curiosity until the 1950s when Powell Richards realized the potential of technetium-99m as a medical radiotracer and promoted its use among the medical community. While Richards was in charge of the radioisotope production at the Hot Lab Division of the Brookhaven National Laboratory, Walter Tucker and Margaret Greene were working on how to improve the separation process purity of the short-lived eluted daughter product iodine-132 from tellurium-132, its 3.2-days parent, produced in the Brookhaven Graphite Research Reactor. They detected a trace contaminant which proved to be Tc-99m, which was coming from Mo-99 and was following tellurium in the chemistry of the separation process for other fission products. Based on the similarities between the chemistry of the tellurium-iodine parent-daughter pair, Tucker and Greene developed the first technetium-99m generator in 1958. It was not until 1960 that Richards became the first to suggest the idea of using technetium as a medical tracer.

The first US publication to report on medical scanning of Tc-99m appeared in August 1963. Sorensen and Archambault demonstrated that intravenously injected carrier-free Mo-99 selectively and efficiently concentrated in the liver, becoming an internal generator of Tc-99m. After build-up of Tc-99m, they could visualize the liver using the 140 keV gamma ray emission.

Worldwide expansion

The production and medical use of Tc-99m rapidly expanded across the world in the 1960s, benefiting from the development and continuous improvements of the gamma cameras.
Americas
Between 1963 and 1966, numerous scientific studies demonstrated the use of Tc-99m as radiotracer or diagnostic tool. As a consequence the demand for Tc-99m grew exponentially and by 1966, Brookhaven National Laboratory was unable to cope with the demand. Production and distribution of Tc-99m generators were transferred to private companies. "TechneKow-CS generator", the first commercial Tc-99m generator, was produced by Nuclear Consultants, Inc. (St. Louis, Missouri) and Union Carbide Nuclear Corporation (Tuxedo, New York). From 1967 to 1984, Mo-99 was produced for Mallinckrodt Nuclear Company at the Missouri University Research Reactor (MURR).

Union Carbide actively developed a process to produce and separate useful isotopes like Mo-99 from mixed fission products that resulted from the irradiation of highly enriched uranium (HEU) targets in nuclear reactors developed from 1968 to 1972 at the Cintichem facility (formerly the Union Carbide Research Center built in the Sterling forest in Tuxedo, New York (41°14′6.88″N 74°12′50.78″W)). The Cintichem process originally used 93% highly enriched U-235 deposited as UO2 on the inside of a cylindrical target.

At the end of the 1970s, 200,000 Ci (7.4×1015 Bq) of total fission product radiation were extracted weekly from 20-30 reactor bombarded HEU capsules, using the so-called "Cintichem [chemical isolation] process." The research facility with its 1961 5-MW pool-type research reactor was later sold to Hoffman-LaRoche and became Cintichem Inc. In 1980, Cintichem, Inc. began the production/isolation of Mo-99 in its reactor, and became the single U.S. producer of Mo-99 during the 1980s. However, in 1989, Cintichem detected an underground leak of radioactive products that led to the reactor shutdown and decommissioning, putting an end to the commercial production of Mo-99 in the USA.

The production of Mo-99 started in Canada in the early 1970s and was shifted to the NRU reactor in the mid 1970s. By 1978 the reactor provided technetium-99m in large enough quantities that were processed by AECL's radiochemical division, which was privatized in 1988 as Nordion, now MDS Nordion. In the 1990s a substitution for the aging NRU reactor for production of radioisotopes was planned. The Multipurpose Applied Physics Lattice Experiment (MAPLE) was designed as a dedicated isotope-production facility. Initially, two identical MAPLE reactors were to be built at Chalk River Laboratories, each capable of supplying 100% of the world's medical isotope demand. However, problems with the MAPLE 1 reactor, most notably a positive power co-efficient of reactivity, led to the cancellation of the project in 2008.

The first commercial Tc-99m generators were produced in Argentina in 1967, with Mo-99 produced in the CNEA's RA-1 Enrico Fermi reactor. Besides its domestic market CNEA supplies Mo-99 to some South American countries.
Asia
In 1967, the first Tc-99m procedures were carried out in Auckland, New Zealand. Mo-99 was initially supplied by Amersham, UK, then by the Australian Nuclear Science and Technology Organisation (ANSTO) in Lucas Heights, Australia.
Europe
In May 1963, Scheer and Maier-Borst were the first to introduce the use of Tc-99m for medical applications. In 1968, Philips-Duphar (later Mallinckrodt, today Covidien) marketed the first technetium-99m generator produced in Europe and distributed from Petten, the Netherlands.

Shortage

Global shortages of technetium-99m emerged in the late 2000s because two aging nuclear reactors (NRU and HFR) that provided about two-thirds of the world’s supply of molybdenum-99, which itself has a half-life of only 66 hours, were shut down repeatedly for extended maintenance periods. In May 2009 the Atomic Energy of Canada Limited announced the detection of a small leak of heavy water in the NRU reactor that remained out of service until completion of the repairs in August 2010. After the observation of gas bubble jets released from one of the deformations of primary cooling water circuits in August 2008, the HFR reactor was stopped for a thorough safety investigation. NRG received in February 2009 a temporary license to operate HFR only when necessary for medical radioisotope production. HFR stopped for repairs at the beginning of 2010 and was restarted in September 2010.

Two replacement Canadian reactors constructed in the 1990s were closed before beginning operation, for safety reasons. A construction permit for a new production facility to be built in Columbia, MO was issued in May 2018.

Nuclear properties

Technetium-99m is a metastable nuclear isomer, as indicated by the "m" after its mass number 99. This means it is a decay product whose nucleus remains in an excited state that lasts much longer than is typical. The nucleus will eventually relax (i.e., de-excite) to its ground state through the emission of gamma rays or internal conversion electrons. Both of these decay modes rearrange the nucleons without transmuting the technetium into another element. 

Tc-99m decays mainly by gamma emission, slightly less than 88% of the time. (99mTc → 99Tc + γ) About 98.6% of these gamma decays result in 140.5 keV gamma rays and the remaining 1.4% are to gammas of a slightly higher energy at 142.6 keV. These are the radiations that are picked up by a gamma camera when 99mTc is used as a radioactive tracer for medical imaging. The remaining approximately 12% of 99mTc decays are by means of internal conversion, resulting in ejection of high speed internal conversion electrons in several sharp peaks (as is typical of electrons from this type of decay) also at about 140 keV (99mTc → 99Tc+ + e). These conversion electrons will ionize the surrounding matter like beta radiation electrons would do, contributing along with the 140.5 keV and 142.6 keV gammas to the total deposited dose.

Pure gamma emission is the desirable decay mode for medical imaging because other particles deposit more energy in the patient body (radiation dose) than in the camera. Metastable isomeric transition is the only nuclear decay mode that approaches pure gamma emission. 

Tc-99m's half-life of 6.0058 hours is considerably longer (by 14 orders of magnitude, at least) than most nuclear isomers, though not unique. This is still a short half-life relative to many other known modes of radioactive decay and it is in the middle of the range of half lives for radiopharmaceuticals used for medical imaging

After gamma emission or internal conversion, the resulting ground-state technetium-99 then decays with a half-life of 211,000 years to stable ruthenium-99. This process emits soft beta radiation without a gamma. Such low radioactivity from the daughter product(s) is a desirable feature for radiopharmaceuticals.

Production

Production of Mo-99 in nuclear reactors

Neutron irradiation of U-235 targets
The parent nuclide of Tc-99m, Mo-99, is mainly extracted for medical purposes from the fission products created in neutron-irradiated U-235 targets, the majority of which is produced in five nuclear research reactors around the world using highly enriched uranium (HEU) targets. Smaller amounts of 99Mo are produced from low-enriched uranium in at least three reactors.
Nuclear reactors producing 99Mo from U-235 targets. The year indicates the date of the first criticality of the reactor.
Type Reactor Location Target/Fuel Year
Large-scale producers NRU Canada HEU/LEU 1957
BR2 Belgium HEU/HEU 1961
SAFARI-1 South Africa LEU/LEU 1965
HFR the Netherlands HEU/LEU 1961
Osiris reactor France LEU/HEU 1966
Regional producers OPAL Australia LEU/LEU 2006
MPR RSG-GAS Indonesia LEU/LEU 1987
RA-3 Argentina LEU/LEU 1961
MARIA Poland HEU/HEU 1974
LVR-15 Czech Republic HEU/HEU 1957
Neutron activation of Mo-98
Production of 99Mo by neutron activation of natural molybdenum, or molybdenum enriched in Mo-98, is another, currently smaller, route of production.

Production of Tc-99m/Mo-99 in particle accelerators

Production of "Instant" Tc-99m
The feasibility of Tc-99m production with the 22-MeV-proton bombardment of a Mo-100 target in medical cyclotrons was demonstrated in 1971. The recent shortages of Tc-99m reignited the interest in the production of "instant" 99mTc by proton bombardment of isotopically enriched Mo-100 targets (>99.5%) following the reaction 100Mo(p,2n)99mTc. Canada is commissioning such cyclotrons, designed by Advanced Cyclotron Systems, for Tc-99m production at the University of Alberta and the Université de Sherbrooke, and is planning others at the University of British Columbia, TRIUMF, University of Saskatchewan and Lakehead University.
Indirect routes of production of Mo-99
Other particle accelerator-based isotope production techniques have been investigated. The supply disruptions of Mo-99 in the late 2000s and the aging of the producing nuclear reactors forced the industry to look into alternative methods of production. The use of cyclotrons to produce Mo-99 from Mo-100 via (n,2n) or (γ,n) reactions has been further investigated.

Technetium-99m generators

Technetium-99m's short half-life of 6 hours makes storage impossible and would make transport very expensive. It is instead its parent nuclide 99Mo is supplied to hospitals after its extraction from the neutron-irradiated uranium targets and its purification in dedicated processing facilities. It is shipped by specialised radiopharmaceutical companies in the form of technetium-99m generators worldwide or directly distributed to the local market. The generators, colloquially known as a moly cows, are devices designed to provide radiation shielding for transport and to minimize the extraction work done at the medical facility. A typical dose rate at 1 metre from Tc-99m generator is 20-50 μSv/h during transport. These generators' output declines with time and must be replaced weekly, since the half-life of 99Mo is still only 66 hours.

Molybdenum-99 spontaneously decays to excited states of 99Tc through beta decay. Over 87% of the decays lead to the 142 keV excited state of Tc-99m. A
β
electron and a
ν
e
electron antineutrino are emitted in the process (99Mo → 99mTc +
β
+
ν
e
). The
β
electrons are easily shielded for transport, and 99mTc generators are only minor radiation hazards, mostly due to secondary X-rays produced by the electrons (also known as Bremsstrahlung). 

At the hospital, the 99mTc that forms through 99Mo decay is chemically extracted from the technetium-99m generator. Most commercial 99Mo/99mTc generators use column chromatography, in which 99Mo in the form of water-soluble molybdate, MoO42− is adsorbed onto acid alumina (Al2O3). When the 99Mo decays, it forms pertechnetate TcO4, which, because of its single charge, is less tightly bound to the alumina. Pulling normal saline solution through the column of immobilized 99MoO42− elutes the soluble 99mTcO4, resulting in a saline solution containing the 99mTc as the dissolved sodium salt of the pertechnetate. One technetium-99m generator, holding only a few micrograms of 99Mo, can potentially diagnose 10,000 patients because it will be producing 99mTc strongly for over a week.

Technetium scintigraphy of a neck of a Graves' disease patient

Preparation

Technetium exits the generator in the form of the pertechnetate ion, TcO4. The oxidation state of Tc in this compound is +7. This is directly suitable for medical applications only in bone scans (it is taken up by osteoblasts) and some thyroid scans (it is taken up in place of iodine by normal thyroid tissues). In other types of scans relying on Tc-99m, a reducing agent is added to the pertechnetate solution to bring the oxidation state of the Tc down to +3 or +4. Secondly, a ligand is added to form a coordination complex. The ligand is chosen to have an affinity for the specific organ to be targeted. For example, the exametazime complex of Tc in oxidation state +3 is able to cross the blood–brain barrier and flow through the vessels in the brain for cerebral blood flow imaging. Other ligands include sestamibi for myocardial perfusion imaging and mercapto acetyl triglycine for MAG3 scan to measure renal function.

Medical uses

In 1970, Eckelman and Richards presented the first "kit" containing all the ingredients required to release the Tc-99m, "milked" from the generator, in the chemical form to be administered to the patient.

Technetium-99m is used in 20 million diagnostic nuclear medical procedures every year. Approximately 85% of diagnostic imaging procedures in nuclear medicine use this isotope as radioactive tracer. Klaus Schwochau's book Technetium lists 31 radiopharmaceuticals based on 99mTc for imaging and functional studies of the brain, myocardium, thyroid, lungs, liver, gallbladder, kidneys, skeleton, blood, and tumors. Depending on the procedure, the 99mTc is tagged (or bound to) a pharmaceutical that transports it to its required location. For example, when 99mTc is chemically bound to exametazime (HMPAO), the drug is able to cross the blood–brain barrier and flow through the vessels in the brain for cerebral blood-flow imaging. This combination is also used for labeling white blood cells (99mTc labeled WBC) to visualize sites of infection. 99mTc sestamibi is used for myocardial perfusion imaging, which shows how well the blood flows through the heart. Imaging to measure renal function is done by attaching 99mTc to mercaptoacetyl triglycine (MAG3); this procedure is known as a MAG3 scan.

Technetium-99m can be readily detected in the body by medical equipment because it emits 140.5 keV gamma rays (these are about the same wavelength as emitted by conventional X-ray diagnostic equipment), and its half-life for gamma emission is six hours (meaning 94% of it decays to 99Tc in 24 hours). The "short" physical half-life of the isotope and its biological half-life of 1 day (in terms of human activity and metabolism) allows for scanning procedures which collect data rapidly, but keep total patient radiation exposure low.

Radiation side-effects

Diagnostic treatment involving technetium-99m will result in radiation exposure to technicians, patients, and passers-by. Typical quantities of technetium administered for immunoscintigraphy tests, such as SPECT tests, range from 400 to 1,100 MBq (11 to 30 mCi) (millicurie or mCi; and Mega-Becquerel or MBq) for adults. These doses result in radiation exposures to the patient around 10 mSv (1000 mrem), the equivalent of about 500 chest X-ray exposures. This level of radiation exposure carries a 1 in 1000 lifetime risk of developing a solid cancer or leukemia in the patient. The risk is higher in younger patients, and lower in older ones. Unlike a chest x-ray, the radiation source is inside the patient and will be carried around for a few days, exposing others to second-hand radiation. A spouse who stays constantly by the side of the patient through this time might receive one thousandth of patient's radiation dose this way. 

The short half-life of the isotope allows for scanning procedures that collect data rapidly. The isotope is also of a very low energy level for a gamma emitter. Its ~140 keV of energy make it safer for use because of the substantially reduced ionization compared with other gamma emitters. The energy of gammas from 99mTc is about the same as the radiation from a commercial diagnostic X-ray machine, although the number of gammas emitted results in radiation doses more comparable to X-ray studies like computed tomography

Technetium-99m has several features that make it safer than other possible isotopes. Its gamma decay mode can be easily detected by a camera, allowing the use of smaller quantities. And because technetium-99m has a short half-life, its quick decay into the far less radioactive technetium-99 results in relatively low total radiation dose to the patient per unit of initial activity after administration, as compared to other radioisotopes. In the form administered in these medical tests (usually pertechnetate), technetium-99m and technetium-99 are eliminated from the body within a few days.

3-D scanning technique: SPECT

Single photon emission computed tomography (SPECT) is a nuclear medicine imaging technique using gamma rays. It may be used with any gamma-emitting isotope, including Tc-99m. In the use of technetium-99m, the radioisotope is administered to the patient and the escaping gamma rays are incident upon a moving gamma camera which computes and processes the image. To acquire SPECT images, the gamma camera is rotated around the patient. Projections are acquired at defined points during the rotation, typically every three to six degrees. In most cases, a full 360° rotation is used to obtain an optimal reconstruction. The time taken to obtain each projection is also variable, but 15–20 seconds are typical. This gives a total scan time of 15–20 minutes.

The technetium-99m radioisotope is used predominantly in bone and brain scans. For bone scans, the pertechnetate ion is used directly, as it is taken up by osteoblasts attempting to heal a skeletal injury, or (in some cases) as a reaction of these cells to a tumor (either primary or metastatic) in the bone. In brain scanning, Tc-99m is attached to the chelating agent HMPAO to create technetium (99mTc) exametazime, an agent which localizes in the brain according to region blood flow, making it useful for the detection of stroke and dementing illnesses that decrease regional brain flow and metabolism.
Most recently, technetium-99m scintigraphy has been combined with CT coregistration technology to produce SPECT/CT scans. These employ the same radioligands and have the same uses as SPECT scanning, but are able to provide even finer 3-D localization of high-uptake tissues, in cases where finer resolution is needed. An example is the sestamibi parathyroid scan which is performed using the Tc-99m radioligand sestamibi, and can be done in either SPECT or SPECT/CT machines.

Bone scan

The nuclear medicine technique commonly called the bone scan usually uses Tc-99m. It is not to be confused with the "bone density scan", DEXA, which is a low-exposure X-ray test measuring bone density to look for osteoporosis and other diseases where bones lose mass without rebuilding activity. The nuclear medicine technique is sensitive to areas of unusual bone rebuilding activity, since the radiopharmaceutical is taken up by osteoblast cells which build bone. The technique therefore is sensitive to fractures and bone reaction to bone tumors, including metastases. For a bone scan, the patient is injected with a small amount of radioactive material, such as 700–1,100 MBq (19–30 mCi) of 99mTc-medronic acid and then scanned with a gamma camera. Medronic acid is a phosphate derivative which can exchange places with bone phosphate in regions of active bone growth, so anchoring the radioisotope to that specific region. To view small lesions (less than 1 centimetre (0.39 in)) especially in the spine, the SPECT imaging technique may be required, but currently in the United States, most insurance companies require separate authorization for SPECT imaging.

Myocardial perfusion imaging

Myocardial perfusion imaging (MPI) is a form of functional cardiac imaging, used for the diagnosis of ischemic heart disease. The underlying principle is, under conditions of stress, diseased myocardium receives less blood flow than normal myocardium. MPI is one of several types of cardiac stress test. As a nuclear stress test the average radiation exposure is 9.4 mSV which compared to a typical 2 view Chest X-Ray (.1 mSV) is equivalent to 94 Chest X-Rays.

Several radiopharmaceuticals and radionuclides may be used for this, each giving different information. In the myocardial perfusion scans using Tc-99m, the radiopharmaceuticals 99mTc-tetrofosmin (Myoview, GE Healthcare) or 99mTc-sestamibi (Cardiolite, Bristol-Myers Squibb) are used. Following this, myocardial stress is induced, either by exercise or pharmacologically with adenosine, dobutamine or dipyridamole(Persantine), which increase the heart rate or by regadenoson(Lexiscan), a vasodilator. (Aminophylline can be used to reverse the effects of dipyridamole and regadenoson). Scanning may then be performed with a conventional gamma camera, or with SPECT/CT.

Cardiac ventriculography

In cardiac ventriculography, a radionuclide, usually 99mTc, is injected, and the heart is imaged to evaluate the flow through it, to evaluate coronary artery disease, valvular heart disease, congenital heart diseases, cardiomyopathy, and other cardiac disorders. As a nuclear stress test the average radiation exposure is 9.4 mSV which compared to a typical 2 view Chest X-Ray (.1 mSV) is equivalent to 94 Chest X-Rays. It exposes patients to less radiation than to comparable chest X-ray studies.

Functional brain imaging

Usually the gamma-emitting tracer used in functional brain imaging is 99mTc-HMPAO (hexamethylpropylene amine oxime, exametazime). The similar 99mTc-EC tracer may also be used. These molecules are preferentially distributed to regions of high brain blood flow, and act to assess brain metabolism regionally, in an attempt to diagnose and differentiate the different causal pathologies of dementia. When used with the 3-D SPECT technique, they compete with brain FDG-PET scans and fMRI brain scans as techniques to map the regional metabolic rate of brain tissue.

Sentinel-node identification

The radioactive properties of 99mTc can be used to identify the predominant lymph nodes draining a cancer, such as breast cancer or malignant melanoma. This is usually performed at the time of biopsy or resection.99mTc-labelled isosulfan blue dye is injected intradermally around the intended biopsy site. The general location of the sentinel node is determined with the use of a handheld scanner with a gamma-sensor probe that detects the technetium-99m–labeled sulfur colloid that was previously injected around the biopsy site. An incision is then made over the area of highest radionuclide accumulation, and the sentinel node is identified within the incision by inspection; the isosulfan blue dye will usually stain any draining nodes blue.

Immunoscintigraphy

Immunoscintigraphy incorporates 99mTc into a monoclonal antibody, an immune system protein, capable of binding to cancer cells. A few hours after injection, medical equipment is used to detect the gamma rays emitted by the 99mTc; higher concentrations indicate where the tumor is. This technique is particularly useful for detecting hard-to-find cancers, such as those affecting the intestines. These modified antibodies are sold by the German company Hoechst (now part of Sanofi-Aventis) under the name "Scintium".

Blood pool labeling

When 99mTc is combined with a tin compound, it binds to red blood cells and can therefore be used to map circulatory system disorders. It is commonly used to detect gastrointestinal bleeding sites as well as ejection fraction, heart wall motion abnormalities, abnormal shunting, and to perform ventriculography.

Pyrophosphate for heart damage

A pyrophosphate ion with 99mTc adheres to calcium deposits in damaged heart muscle, making it useful to gauge damage after a heart attack.

Sulfur colloid for spleen scan

The sulfur colloid of 99mTc is scavenged by the spleen, making it possible to image the structure of the spleen.

Meckel's diverticulum

Pertechnetate is actively accumulated and secreted by the mucoid cells of the gastric mucosa, and therefore, technetate(VII) radiolabeled with Tc99m is injected into the body when looking for ectopic gastric tissue as is found in a Meckel's diverticulum with Meckel's Scans.

Thallium

From Wikipedia, the free encyclopedia

Thallium,  81Tl
Thallium pieces in ampoule.jpg
Thallium
Pronunciation/ˈθæliəm/ (THAL-ee-əm)
Appearancesilvery white
Standard atomic weight Ar, std(Tl)[204.382204.385] conventional: 204.38
Thallium in the periodic table
Hydrogen
Helium
Lithium Beryllium
Boron Carbon Nitrogen Oxygen Fluorine Neon
Sodium Magnesium
Aluminium Silicon Phosphorus Sulfur Chlorine Argon
Potassium Calcium Scandium
Titanium Vanadium Chromium Manganese Iron Cobalt Nickel Copper Zinc Gallium Germanium Arsenic Selenium Bromine Krypton
Rubidium Strontium Yttrium

Zirconium Niobium Molybdenum Technetium Ruthenium Rhodium Palladium Silver Cadmium Indium Tin Antimony Tellurium Iodine Xenon
Caesium Barium Lanthanum Cerium Praseodymium Neodymium Promethium Samarium Europium Gadolinium Terbium Dysprosium Holmium Erbium Thulium Ytterbium Lutetium Hafnium Tantalum Tungsten Rhenium Osmium Iridium Platinum Gold Mercury (element) Thallium Lead Bismuth Polonium Astatine Radon
Francium Radium Actinium Thorium Protactinium Uranium Neptunium Plutonium Americium Curium Berkelium Californium Einsteinium Fermium Mendelevium Nobelium Lawrencium Rutherfordium Dubnium Seaborgium Bohrium Hassium Meitnerium Darmstadtium Roentgenium Copernicium Nihonium Flerovium Moscovium Livermorium Tennessine Oganesson
In

Tl

Nh
mercurythalliumlead
Atomic number (Z)81
Groupgroup 13 (boron group)
Periodperiod 6
Blockp-block
Element category  post-transition metal
Electron configuration[Xe] 4f14 5d10 6s2 6p1
Electrons per shell
2, 8, 18, 32, 18, 3
Physical properties
Phase at STPsolid
Melting point577 K ​(304 °C, ​579 °F)
Boiling point1746 K ​(1473 °C, ​2683 °F)
Density (near r.t.)11.85 g/cm3
when liquid (at m.p.)11.22 g/cm3
Heat of fusion4.14 kJ/mol
Heat of vaporization165 kJ/mol
Molar heat capacity26.32 J/(mol·K)
Vapor pressure
P (Pa) 1 10 100 1 k 10 k 100 k
at T (K) 882 977 1097 1252 1461 1758
Atomic properties
Oxidation states−5, −2, −1, +1, +2, +3 (a mildly basic oxide)
ElectronegativityPauling scale: 1.62
Ionization energies
  • 1st: 589.4 kJ/mol
  • 2nd: 1971 kJ/mol
  • 3rd: 2878 kJ/mol

Atomic radiusempirical: 170 pm
Covalent radius145±7 pm
Van der Waals radius196 pm
Color lines in a spectral range
Spectral lines of thallium
Other properties
Natural occurrenceprimordial
Crystal structurehexagonal close-packed (hcp)
Hexagonal close packed crystal structure for thallium
Speed of sound thin rod818 m/s (at 20 °C)
Thermal expansion29.9 µm/(m·K) (at 25 °C)
Thermal conductivity46.1 W/(m·K)
Electrical resistivity0.18 µΩ·m (at 20 °C)
Magnetic orderingdiamagnetic
Magnetic susceptibility−50.9·10−6 cm3/mol (298 K)[3]
Young's modulus8 GPa
Shear modulus2.8 GPa
Bulk modulus43 GPa
Poisson ratio0.45
Mohs hardness1.2
Brinell hardness26.5–44.7 MPa
CAS Number7440-28-0
History
Namingafter Greek thallos, green shoot or twig
DiscoveryWilliam Crookes (1861)
First isolationClaude-Auguste Lamy (1862)
Main isotopes of thallium
Iso­tope Abun­dance Half-life (t1/2) Decay mode Pro­duct
203Tl 29.5% stable
204Tl syn 3.78 y β 204Pb
ε 204Hg
205Tl 70.5% stable

Thallium is a chemical element with symbol Tl and atomic number 81. It is a gray post-transition metal that is not found free in nature. When isolated, thallium resembles tin, but discolors when exposed to air. Chemists William Crookes and Claude-Auguste Lamy discovered thallium independently in 1861, in residues of sulfuric acid production. Both used the newly developed method of flame spectroscopy, in which thallium produces a notable green spectral line. Thallium, from Greek θαλλός, thallós, meaning "a green shoot or twig", was named by Crookes. It was isolated by both Lamy and Crookes in 1862; Lamy by electrolysis, and Crookes by precipitation and melting of the resultant powder. Crookes exhibited it as a powder precipitated by zinc at the International exhibition, which opened on 1 May that year.

Thallium tends to oxidize to the +3 and +1 oxidation states as ionic salts. The +3 state resembles that of the other elements in group 13 (boron, aluminium, gallium, indium). However, the +1 state, which is far more prominent in thallium than the elements above it, recalls the chemistry of alkali metals, and thallium(I) ions are found geologically mostly in potassium-based ores, and (when ingested) are handled in many ways like potassium ions (K+) by ion pumps in living cells.

Commercially, thallium is produced not from potassium ores, but as a byproduct from refining of heavy-metal sulfide ores. Approximately 60–70% of thallium production is used in the electronics industry, and the remainder is used in the pharmaceutical industry and in glass manufacturing.[6] It is also used in infrared detectors. The radioisotope thallium-201 (as the soluble chloride TlCl) is used in small, nontoxic amounts as an agent in a nuclear medicine scan, during one type of nuclear cardiac stress test.

Soluble thallium salts (many of which are nearly tasteless) are toxic, and they were historically used in rat poisons and insecticides. Use of these compounds has been restricted or banned in many countries, because of their nonselective toxicity. Thallium poisoning usually results in hair loss, although this characteristic symptom does not always surface. Because of its historic popularity as a murder weapon, thallium has gained notoriety as "the poisoner's poison" and "inheritance powder" (alongside arsenic).

Characteristics

A thallium atom has 81 electrons, arranged in the electron configuration [Xe]4f145d106s26p1; of these, the three outermost electrons in the sixth shell are valence electrons. Due to the inert pair effect, the 6s electron pair is relativistically stabilised and it is more difficult to get them involved in chemical bonding than for the heavier elements. Thus, very few electrons are available for metallic bonding, similar to the neighboring elements mercury and lead, and hence thallium, like its congeners, is a soft, highly electrically conducting metal with a low melting point of 304 °C.

A number of standard electrode potentials, depending on the reaction under study, are reported for thallium, reflecting the greatly decreased stability of the +3 oxidation state:

+0.73 Tl3+ + 3 e ↔ Tl
−0.336 Tl+ + e ↔ Tl

Thallium is the first element in group 13 where the reduction of the +3 oxidation state to the +1 oxidation state is spontaneous under standard conditions. Since bond energies decrease down the group, with thallium, the energy released in forming two additional bonds and attaining the +3 state is not always enough to outweigh the energy needed to involve the 6s-electrons. Accordingly, thallium(I) oxide and hydroxide are more basic and thallium(III) oxide and hydroxide are more acidic, showing that thallium conforms to the general rule of elements being more electropositive in their lower oxidation states.

Thallium is malleable and sectile enough to be cut with a knife at room temperature. It has a metallic luster that, when exposed to air, quickly tarnishes to a bluish-gray tinge, resembling lead. It may be preserved by immersion in oil. A heavy layer of oxide builds up on thallium if left in air. In the presence of water, thallium hydroxide is formed. Sulfuric and nitric acids dissolve thallium rapidly to make the sulfate and nitrate salts, while hydrochloric acid forms an insoluble thallium(I) chloride layer.

Isotopes

Thallium has 25 isotopes which have atomic masses that range from 184 to 210. 203Tl and 205Tl are the only stable isotopes and make up nearly all of natural thallium. 204Tl is the most stable radioisotope, with a half-life of 3.78 years. It is made by the neutron activation of stable thallium in a nuclear reactor. The most useful radioisotope, 201Tl (half-life 73 hours), decays by electron capture, emitting X-rays (~70–80 keV), and photons of 135 and 167 keV in 10% total abundance; therefore, it has good imaging characteristics without excessive patient radiation dose. It is the most popular isotope used for thallium nuclear cardiac stress tests.

Compounds

Thallium(III)

Thallium(III) compounds resemble the corresponding aluminium(III) compounds. They are moderately strong oxidizing agents and are usually unstable, as illustrated by the positive reduction potential for the Tl3+/Tl couple. Some mixed-valence compounds are also known, such as Tl4O3 and TlCl2, which contain both thallium(I) and thallium(III). Thallium(III) oxide, Tl2O3, is a black solid which decomposes above 800 °C, forming the thallium(I) oxide and oxygen.
 
The simplest possible thallium compound, thallane (TlH3), is too unstable to exist in bulk, both due to the instability of the +3 oxidation state as well as poor overlap of the valence 6s and 6p orbitals of thallium with the 1s orbital of hydrogen. The trihalides are more stable, although they are chemically distinct from those of the lighter group 13 elements and are still the least stable in the whole group. For instance, thallium(III) fluoride, TlF3, has the β-BiF3 structure rather than that of the lighter group 13 trifluorides, and does not form the TlF
4
complex anion in aqueous solution. The trichloride and tribromide disproportionate just above room temperature to give the monohalides, and thallium triiodide contains the linear triiodide anion (I
3
) and is actually a thallium(I) compound. Thallium(III) sesquichalcogenides do not exist.

Thallium(I)

The thallium(I) halides are stable. In keeping with the large size of the Tl+ cation, the chloride and bromide have the caesium chloride structure, while the fluoride and iodide have distorted sodium chloride structures. Like the analogous silver compounds, TlCl, TlBr, and TlI are photosensitive. The stability of thallium(I) compounds demonstrates its differences from the rest of the group: a stable oxide, hydroxide, and carbonate are known, as are many chalcogenides.

The double salt Tl
4
(OH)
2
CO
3
has been shown to have hydroxyl-centred triangles of thallium, [Tl
3
(OH)]2+
, as a recurring motif throughout its solid structure.

Organothallium compounds

Organothallium compounds tend to be thermally unstable, in concordance with the trend of decreasing thermal stability down group 13. The chemical reactivity of the Tl–C bond is also the lowest in the group, especially for ionic compounds of the type R2TlX. Thallium forms the stable [Tl(CH3)2]+ ion in aqueous solution; like the isoelectronic Hg(CH3)2 and [Pb(CH3)2]2+, it is linear. Trimethylthallium and triethylthallium are, like the corresponding gallium and indium compounds, flammable liquids with low melting points. Like indium, thallium cyclopentadienyl compounds contain thallium(I), in contrast to gallium(III).

History

Thallium (Greek θαλλός, thallos, meaning "a green shoot or twig") was discovered by William Crookes and Claude Auguste Lamy, working independently, both using flame spectroscopy (Crookes was first to publish his findings, on March 30, 1861). The name comes from thallium's bright green spectral emission lines.

After the publication of the improved method of flame spectroscopy by Robert Bunsen and Gustav Kirchhoff and the discovery of caesium and rubidium in the years 1859 to 1860, flame spectroscopy became an approved method to determine the composition of minerals and chemical products. Crookes and Lamy both started to use the new method. Crookes used it to make spectroscopic determinations for tellurium on selenium compounds deposited in the lead chamber of a sulfuric acid production plant near Tilkerode in the Harz mountains. He had obtained the samples for his research on selenium cyanide from August Hofmann years earlier. By 1862, Crookes was able to isolate small quantities of the new element and determine the properties of a few compounds. Claude-Auguste Lamy used a spectrometer that was similar to Crookes' to determine the composition of a selenium-containing substance which was deposited during the production of sulfuric acid from pyrite. He also noticed the new green line in the spectra and concluded that a new element was present. Lamy had received this material from the sulfuric acid plant of his friend Fréd Kuhlmann and this by-product was available in large quantities. Lamy started to isolate the new element from that source. The fact that Lamy was able to work ample quantities of thallium enabled him to determine the properties of several compounds and in addition he prepared a small ingot of metallic thallium which he prepared by remelting thallium he had obtained by electrolysis of thallium salts. 

As both scientists discovered thallium independently and a large part of the work, especially the isolation of the metallic thallium was done by Lamy, Crookes tried to secure his own priority on the work. Lamy was awarded a medal at the International Exhibition in London 1862: For the discovery of a new and abundant source of thallium and after heavy protest Crookes also received a medal: thallium, for the discovery of the new element. The controversy between both scientists continued through 1862 and 1863. Most of the discussion ended after Crookes was elected Fellow of the Royal Society in June 1863.

The dominant use of thallium was the use as poison for rodents. After several accidents the use as poison was banned in the United States by Presidential Executive Order 11643 in February 1972. In subsequent years several other countries also banned its use.

Occurrence and production

Although thallium is a modestly abundant element in the Earth's crust, with a concentration estimated to be about 0.7 mg/kg, mostly in association with potassium-based minerals in clays, soils, and granites, thallium is not generally economically recoverable from these sources. The major source of thallium for practical purposes is the trace amount that is found in copper, lead, zinc, and other heavy-metal-sulfide ores.

A close view of a rock crusted with groups of glassy, lustrous, silvery-blue hutchinsonite, in tight clusters of loosely aligned needle-like crystals, among smaller clusters of tiny orange-brown crystals
Crystals of hutchinsonite (TlPbAs5S9)
 
Thallium is found in the minerals crookesite TlCu7Se4, hutchinsonite TlPbAs5S9, and lorándite TlAsS2. Thallium also occurs as a trace element in iron pyrite, and thallium is extracted as a by-product of roasting this mineral for the production of sulfuric acid.

Thallium can also be obtained from the smelting of lead and zinc ores. Manganese nodules found on the ocean floor contain some thallium, but the collection of these nodules has been prohibitively expensive. There is also the potential for damaging the oceanic environment. In addition, several other thallium minerals, containing 16% to 60% thallium, occur in nature as complexes of sulfides or selenides that primarily contain antimony, arsenic, copper, lead, and/or silver. These minerals are rare, and they have had no commercial importance as sources of thallium. The Allchar deposit in southern Macedonia was the only area where thallium was actively mined. This deposit still contains an estimated 500 tonnes of thallium, and it is a source for several rare thallium minerals, for example lorándite.

The United States Geological Survey (USGS) estimates that the annual worldwide production of thallium is about 10 metric tonnes as a by-product from the smelting of copper, zinc, and lead ores. Thallium is either extracted from the dusts from the smelter flues or from residues such as slag that are collected at the end of the smelting process. The raw materials used for thallium production contain large amounts of other materials and therefore a purification is the first step. The thallium is leached either by the use of a base or sulfuric acid from the material. The thallium is precipitated several times from the solution to remove impurities. At the end it is converted to thallium sulfate and the thallium is extracted by electrolysis on platinum or stainless steel plates. The production of thallium decreased by about 33% in the period from 1995 to 2009 – from about 15 metric tonnes to about 10 tonnes. Since there are several small deposits or ores with relatively high thallium content, it would be possible to increase the production if a new application, such as a hypothetical thallium-containing high-temperature superconductor, becomes practical for widespread use outside of the laboratory.

Applications

Historic uses

The odorless and tasteless thallium sulfate was once widely used as rat poison and ant killer. Since 1972 this use has been prohibited in the United States due to safety concerns. Many other countries followed this example in subsequent years. Thallium salts were used in the treatment of ringworm, other skin infections and to reduce the night sweating of tuberculosis patients. This use has been limited due to their narrow therapeutic index, and the development of improved medicines for these conditions.

Optics

Thallium(I) bromide and thallium(I) iodide crystals have been used as infrared optical materials, because they are harder than other common infrared optics, and because they have transmission at significantly longer wavelengths. The trade name KRS-5 refers to this material. Thallium(I) oxide has been used to manufacture glasses that have a high index of refraction. Combined with sulfur or selenium and arsenic, thallium has been used in the production of high-density glasses that have low melting points in the range of 125 and 150 °C. These glasses have room temperature properties that are similar to ordinary glasses and are durable, insoluble in water and have unique refractive indices.

Electronics

A heavily pitted, blackish cylindrical rod, with extensive, crumbling brown-and-white corrosion
Corroded thallium rod
 
Thallium(I) sulfide's electrical conductivity changes with exposure to infrared light therefore making this compound useful in photoresistors. Thallium selenide has been used in a bolometer for infrared detection. Doping selenium semiconductors with thallium improves their performance, thus it is used in trace amounts in selenium rectifiers. Another application of thallium doping is the sodium iodide crystals in gamma radiation detection devices. In these, the sodium iodide crystals are doped with a small amount of thallium to improve their efficiency as scintillation generators. Some of the electrodes in dissolved oxygen analyzers contain thallium.

High-temperature superconductivity

Research activity with thallium is ongoing to develop high-temperature superconducting materials for such applications as magnetic resonance imaging, storage of magnetic energy, magnetic propulsion, and electric power generation and transmission. The research in applications started after the discovery of the first thallium barium calcium copper oxide superconductor in 1988. Thallium cuprate superconductors have been discovered that have transition temperatures above 120 K. Some mercury-doped thallium-cuprate superconductors have transition temperatures above 130 K at ambient pressure, nearly as high as the world-record-holding mercury cuprates.

Medical

Before the widespread application of technetium-99m in nuclear medicine, the radioactive isotope thallium-201, with a half-life of 73 hours, was the main substance for nuclear cardiography. The nuclide is still used for stress tests for risk stratification in patients with coronary artery disease (CAD). This isotope of thallium can be generated using a transportable generator, which is similar to the technetium-99m generator. The generator contains lead-201 (half-life 9.33 hours), which decays by electron capture to thallium-201. The lead-201 can be produced in a cyclotron by the bombardment of thallium with protons or deuterons by the (p,3n) and (d,4n) reactions.

Thallium stress test

A thallium stress test is a form of scintigraphy in which the amount of thallium in tissues correlates with tissue blood supply. Viable cardiac cells have normal Na+/K+ ion-exchange pumps. The Tl+ cation binds the K+ pumps and is transported into the cells. Exercise or dipyridamole induces widening (vasodilation) of arteries in the body. This produces coronary steal by areas where arteries are maximally dilated. Areas of infarct or ischemic tissue will remain "cold". Pre- and post-stress thallium may indicate areas that will benefit from myocardial revascularization. Redistribution indicates the existence of coronary steal and the presence of ischemic coronary artery disease.

Other uses

A mercury–thallium alloy, which forms a eutectic at 8.5% thallium, is reported to freeze at −60 °C, some 20 °C below the freezing point of mercury. This alloy is used in thermometers and low-temperature switches. In organic synthesis, thallium(III) salts, as thallium trinitrate or triacetate, are useful reagents for performing different transformations in aromatics, ketones and olefins, among others. Thallium is a constituent of the alloy in the anode plates of magnesium seawater batteries. Soluble thallium salts are added to gold plating baths to increase the speed of plating and to reduce grain size within the gold layer.

A saturated solution of equal parts of thallium(I) formate (Tl(CHO2)) and thallium(I) malonate (Tl(C3H3O4)) in water is known as Clerici solution. It is a mobile, odorless liquid which changes from yellowish to colourless upon reducing the concentration of the thallium salts. With a density of 4.25 g/cm3 at 20 °C, Clerici solution is one of the heaviest aqueous solutions known. It was used in the 20th century for measuring the density of minerals by the flotation method, but its use has discontinued due to the high toxicity and corrosiveness of the solution.

Thallium iodide is frequently used as an additive in metal-halide lamps, often together with one or two halides of other metals. It allows optimization of the lamp temperature and color rendering, and shifts the spectral output to the green region, which is useful for underwater lighting.

Toxicity

Thallium
Hazards
GHS pictograms The skull-and-crossbones pictogram in the Globally Harmonized System of Classification and Labelling of Chemicals (GHS)The health hazard pictogram in the Globally Harmonized System of Classification and Labelling of Chemicals (GHS)The environment pictogram in the Globally Harmonized System of Classification and Labelling of Chemicals (GHS)
GHS signal word Danger
H300, H330, H373, H413
P260, P264, P284, P301, P310, P310
NFPA 704
Flammability code 0: Will not burn. E.g., waterHealth code 4: Very short exposure could cause death or major residual injury. E.g., VX gasReactivity code 2: Undergoes violent chemical change at elevated temperatures and pressures, reacts violently with water, or may form explosive mixtures with water. E.g., phosphorusSpecial hazards (white): no codeNFPA 704 four-colored diamond
0
4
2

Thallium and its compounds are extremely toxic, and should be handled with care. There are numerous recorded cases of fatal thallium poisoning. The Occupational Safety and Health Administration (OSHA) has set the legal limit (permissible exposure limit) for thallium exposure in the workplace as 0.1 mg/m2 skin exposure over an 8-hour workday. The National Institute for Occupational Safety and Health (NIOSH) also set a recommended exposure limit (REL) of 0.1 mg/m2 skin exposure over an 8-hour workday. At levels of 15 mg/m2, thallium is immediately dangerous to life and health.

Contact with skin is dangerous, and adequate ventilation should be provided when melting this metal. Thallium(I) compounds have a high aqueous solubility and are readily absorbed through the skin. Exposure by inhalation should not exceed 0.1 mg/m2 in an 8-hour time-weighted average (40-hour work week). Thallium will readily absorb through the skin, and care should be taken to avoid this route of exposure, as cutaneous absorption can exceed the absorbed dose received by inhalation at the permissible exposure limit (PEL). Thallium is a suspected human carcinogen. For a long time thallium compounds were readily available as rat poison. This fact and that it is water-soluble and nearly tasteless led to frequent intoxication caused by accident or criminal intent.

One of the main methods of removing thallium (both radioactive and normal) from humans is to use Prussian blue, a material which absorbs thallium. Up to 20 grams per day of Prussian blue is fed by mouth to the patient, and it passes through their digestive system and comes out in the stool. Hemodialysis and hemoperfusion are also used to remove thallium from the blood serum. At later stages of the treatment, additional potassium is used to mobilize thallium from the tissues.

According to the United States Environmental Protection Agency (EPA), man-made sources of thallium pollution include gaseous emission of cement factories, coal-burning power plants, and metal sewers. The main source of elevated thallium concentrations in water is the leaching of thallium from ore processing operations.

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