Technetium-99m (
99mTc) is a
metastable
In chemistry and physics, metastability denotes an intermediate energetic state within a dynamical system other than the system's state of least energy.
A ball resting in a hollow on a slope is a simple example of metastability. If the ball i ...
nuclear isomer
A nuclear isomer is a metastable state of an atomic nucleus, in which one or more nucleons (protons or neutrons) occupy higher energy levels than in the ground state of the same nucleus. "Metastable" describes nuclei whose excited states have ...
of
technetium-99
Technetium-99 (99Tc) is an isotope of technetium which decays with a half-life of 211,000 years to stable ruthenium-99, emitting beta particles, but no gamma rays. It is the most significant long-lived fission product of uranium fission, produci ...
(itself an isotope of
technetium
Technetium is a chemical element with the symbol Tc and atomic number 43. It is the lightest element whose isotopes are all radioactive. All available technetium is produced as a synthetic element. Naturally occurring technetium is a spontaneous ...
), symbolized as
99mTc, that is used in tens of millions of medical diagnostic procedures annually, making it the most commonly used
medical radioisotope in the world.
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 Kev can refer to:
Given name
* Kev Adams, French comedian, actor, screenwriter and film producer born Kevin Smadja in 1991
* Kevin Kev Carmody (born 1946), Indigenous Australian singer-songwriter
* Kev Coghlan (born 1988), Scottish Grand Prix moto ...
(these 8.8 pm
photon
A photon () is an elementary particle that is a quantum of the electromagnetic field, including electromagnetic radiation such as light and radio waves, and the force carrier for the electromagnetic force. Photons are massless, so they a ...
s 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
Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...
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 unsuitable for therapeutic use.
Technetium-99m was discovered as a product of
cyclotron
A cyclotron is a type of particle accelerator invented by Ernest O. Lawrence in 1929–1930 at the University of California, Berkeley, and patented in 1932. Lawrence, Ernest O. ''Method and apparatus for the acceleration of ions'', filed: Jan ...
bombardment of
molybdenum. This procedure produced
molybdenum-99
Molybdenum (42Mo) has 33 known isotopes, ranging in atomic mass from 83 to 115, as well as four metastable nuclear isomers. Seven isotopes occur naturally, with atomic masses of 92, 94, 95, 96, 97, 98, and 100. All unstable isotopes of molybdenum ...
, a radionuclide with a longer half-life (2.75 days), which decays to
99mTc. This longer decay time allows for
99Mo to be shipped to medical facilities, where
99mTc is extracted from the sample as it is produced. In turn,
99Mo is usually created commercially by fission of
highly enriched uranium in a small number of research and material testing nuclear reactors in several countries.
History
Discovery
In 1938,
Emilio Segrè
Emilio Gino Segrè (1 February 1905 – 22 April 1989) was an Italian-American physicist and Nobel laureate, who discovered the elements technetium and astatine, and the antiproton, a subatomic antiparticle, for which he was awarded the Nobe ...
and
Glenn T. Seaborg isolated for the first time the
metastable isotope technetium-99m, after bombarding natural molybdenum with 8 MeV
deuteron
Deuterium (or hydrogen-2, symbol or deuterium, also known as heavy hydrogen) is one of two stable isotopes of hydrogen (the other being protium, or hydrogen-1). The nucleus of a deuterium atom, called a deuteron, contains one proton and one n ...
s in the
cyclotron
A cyclotron is a type of particle accelerator invented by Ernest O. Lawrence in 1929–1930 at the University of California, Berkeley, and patented in 1932. Lawrence, Ernest O. ''Method and apparatus for the acceleration of ions'', filed: Jan ...
of
Ernest Orlando Lawrence's
Radiation laboratory. In 1970 Seaborg explained that:
Later in 1940, Emilio Segrè and
Chien-Shiung Wu published experimental results of an analysis of fission products of uranium-235, including molybdenum-99, and detected the presence of an isomer of element 43 with a 6-hour half life, later labelled as technetium-99m.
Early medical applications in the United States
99mTc 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
Brookhaven National Laboratory (BNL) is a United States Department of Energy national laboratory located in Upton, Long Island, and was formally established in 1947 at the site of Camp Upton, a former U.S. Army base and Japanese internment c ...
, Walter Tucker and
Margaret Greene were working on how to improve the separation process purity of the short-lived
eluted
In analytical and organic chemistry, elution is the process of extracting one material from another by washing with a solvent; as in washing of loaded ion-exchange resins to remove captured ions.
In a liquid chromatography experiment, for exam ...
daughter product
In nuclear physics, a decay product (also known as a daughter product, daughter isotope, radio-daughter, or daughter nuclide) is the remaining nuclide left over from radioactive decay. Radioactive decay often proceeds via a sequence of steps (de ...
iodine-132 from its parent,
tellurium-132 (with a half life of 3.2 days), produced in the Brookhaven Graphite Research Reactor. They detected a trace contaminant which proved to be
99mTc, which was coming from
99Mo 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
99mTc appeared in August 1963.
Sorensen and Archambault demonstrated that intravenously injected carrier-free
99Mo selectively and efficiently concentrated in the liver, becoming an internal generator of
99mTc. After build-up of
99mTc, they could visualize the liver using the 140 keV gamma ray emission.
Worldwide expansion
The production and medical use of
99mTc 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
99mTc as
radiotracer
A radioactive tracer, radiotracer, or radioactive label is a chemical compound in which one or more atoms have been replaced by a radionuclide so by virtue of its radioactive decay it can be used to explore the mechanism of chemical reactions by tr ...
or diagnostic tool. As a consequence the demand for
99mTc grew exponentially and by 1966,
Brookhaven National Laboratory
Brookhaven National Laboratory (BNL) is a United States Department of Energy national laboratory located in Upton, Long Island, and was formally established in 1947 at the site of Camp Upton, a former U.S. Army base and Japanese internment c ...
was unable to cope with the demand. Production and distribution of
99mTc generators were transferred to private companies. ''"TechneKow-CS generator"'', the first commercial
99mTc generator, was produced by Nuclear Consultants, Inc. (St. Louis, Missouri) and
Union Carbide Nuclear Corporation (Tuxedo, New York). From 1967 to 1984,
99Mo 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
99Mo 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 ()). The Cintichem process originally used 93% highly enriched U-235 deposited as UO
2 on the inside of a cylindrical target.
At the end of the 1970s, of total fission product radiation were extracted weekly from 20-30 reactor bombarded HEU capsules, using the so-called "Cintichem
hemical isolationprocess." 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
99Mo in its reactor, and became the single U.S. producer of
99Mo 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
99Mo in the USA.
The production of
99Mo 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
99mTc generators were produced in
Argentina in 1967, with
99Mo produced in the
CNEA's
RA-1 Enrico Fermi
RA-1 Enrico Fermi is a research reactor in Argentina. It wasd the first nuclear reactor to be built in that country and the first research reactor in the south hemisphere.
Construction started April 1957, with first criticality 20 January 1958. It ...
reactor. Besides its domestic market CNEA supplies
99Mo to some South American countries.
Asia
In 1967, the first
99mTc procedures were carried out in
Auckland
Auckland (pronounced ) ( mi, Tāmaki Makaurau) is a large metropolitan city in the North Island of New Zealand. The most populous urban area in the country and the fifth largest city in Oceania, Auckland has an urban population of about ...
,
New Zealand
New Zealand ( mi, Aotearoa ) is an island country in the southwestern Pacific Ocean. It consists of two main landmasses—the North Island () and the South Island ()—and over 700 smaller islands. It is the sixth-largest island count ...
.
99Mo was initially supplied by Amersham, UK, then by the Australian Nuclear Science and Technology Organisation (
ANSTO
The Australian Nuclear Science and Technology Organisation (ANSTO) is a statutory body of the Australian government, formed in 1987 to replace the Australian Atomic Energy Commission. Its head office and main facilities are in southern outs ...
) in Lucas Heights, Australia.
Europe
In May 1963, Scheer and Maier-Borst were the first to introduce the use of
99mTc 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
Atomic Energy of Canada Limited (AECL) is a Canadian federal Crown corporation and Canada's largest nuclear science and technology laboratory. AECL developed the CANDU reactor technology starting in the 1950s, and in October 2011 licensed this ...
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 (see
MAPLE Reactor) 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
A nuclear isomer is a metastable state of an atomic nucleus, in which one or more nucleons (protons or neutrons) occupy higher energy levels than in the ground state of the same nucleus. "Metastable" describes nuclei whose excited states have ...
, as indicated by the "m" after its
mass number
The mass number (symbol ''A'', from the German word ''Atomgewicht'' tomic weight, also called atomic mass number or nucleon number, is the total number of protons and neutrons (together known as nucleons) in an atomic nucleus. It is approxima ...
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
nucleon
In physics and chemistry, a nucleon is either a proton or a neutron, considered in its role as a component of an atomic nucleus. The number of nucleons in a nucleus defines the atom's mass number (nucleon number).
Until the 1960s, nucleons were ...
s without
transmuting the technetium into another element.
99mTc 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
Internal conversion is a non-radioactive, atomic decay process where an excited nucleus interacts electromagnetically with one of the orbital electrons of an atom. This causes the electron to be emitted (ejected) from the atom. Thus, in internal ...
, 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
Ionization, or Ionisation is the process by which an atom or a molecule acquires a negative or positive charge by gaining or losing electrons, often in conjunction with other chemical changes. The resulting electrically charged atom or molecule ...
the surrounding matter like
beta radiation
A beta particle, also called beta ray or beta radiation (symbol β), is a high-energy, high-speed electron or positron emitted by the radioactive decay of an atomic nucleus during the process of beta decay. There are two forms of beta decay, β� ...
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.
99mTc'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
radiopharmaceutical
Radiopharmaceuticals, or medicinal radiocompounds, are a group of pharmaceutical drugs containing radioactive isotopes. Radiopharmaceuticals can be used as diagnostic and therapeutic agents. Radiopharmaceuticals emit radiation themselves, which ...
s 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.
:
^_Tc -> ce\ce] ^_Tc -> ce211,000\ \ce] \overbrace^
Production
Production of 99Mo in nuclear reactors
Neutron irradiation of U-235 targets
The
daughter product, parent nuclide of
99mTc,
99Mo, 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 reactor
Research reactors are nuclear fission-based nuclear reactors that serve primarily as a neutron source. They are also called non-power reactors, in contrast to power reactors that are used for electricity production, heat generation, or marit ...
s around the world using
highly enriched uranium (HEU) targets. Smaller amounts of
99Mo are produced from
low-enriched uranium in at least three reactors.
Neutron activation of 98Mo
Production of
99Mo by
neutron activation of natural molybdenum, or molybdenum enriched in
98Mo, is another, currently smaller, route of production.
Production of 99mTc/99Mo in particle accelerators
Production of "Instant" 99mTc
The feasibility of
99mTc production with the 22-MeV-proton bombardment of a
100Mo target in medical cyclotrons was demonstrated in 1971. The recent shortages of
99mTc reignited the interest in the production of "instant" 99mTc by proton bombardment of isotopically enriched
100Mo targets (>99.5%) following the reaction
100Mo(p,2n)
99mTc. Canada is commissioning such cyclotrons, designed by
Advanced Cyclotron Systems, for
99mTc production at the
University of Alberta and the
Université de Sherbrooke
The University of Sherbrooke (French: Université de Sherbrooke) (UdS) is a large public French-language university in Quebec, Canada with campuses located in Sherbrooke and Longueuil, a suburb of Montreal approximately west of Sherbrooke. It i ...
, and is planning others at the
University of British Columbia,
TRIUMF,
University of Saskatchewan and
Lakehead University
Lakehead University is a public research university with campuses in Thunder Bay and Orillia, Ontario, Canada. Lakehead University, shortened to 'Lakehead U', is non-denominational and provincially supported. It has undergraduate programs, gradua ...
.
A particular drawback of cyclotron production via (p,2n) on
100Mo is the significant co-production of
99gTc. The preferential in-growth of this nuclide occurs due to the larger reaction cross-section pathway leading to the ground state, which is almost five times higher at the cross-section maximum in comparison with the metastable one at the same energy. Depending on the time required to process the target material and recovery of
99mTc, the amount of
99mTc relative to
99gTc will continue to decrease, in turn reducing the specific activity of
99mTc available. It has been reported that ingrowth of
99gTc as well as the presence of other Tc isotopes can negatively affect subsequent labelling and/or imaging; however, the use of high purity
100Mo targets, specified proton beam energies, and appropriate time of use have shown to be sufficient for yielding
99mTc from a cyclotron comparable to that from a commercial generator. Liquid metal molybdenum-containing targets have been proposed that would aid in streamlined processing, ensuring better production yields. A particular problem associated with the continued reuse of recycled, enriched
100Mo targets is unavoidable transmutation of the target as other Mo isotopes are generated during irradiation and cannot be easily removed post-processing.
Indirect routes of production of 99Mo
Other particle accelerator-based isotope production techniques have been investigated. The supply disruptions of
99Mo in the late 2000s and the ageing of the producing nuclear reactors forced the industry to look into alternative methods of production. The use of cyclotrons or electron accelerators to produce
99Mo from
100Mo via (p,pn) or (γ,n) reactions, respectively, has been further investigated. The (n,2n) reaction on
100Mo yields a higher reaction cross-section for high energy neutrons than of (n,γ) on
98Mo with thermal neutrons. In particular, this method requires accelerators that generate fast neutron spectrums, such as ones using D-T or other fusion-based reactions, or high energy spallation or knock out reactions. A disadvantage of these techniques is the necessity for enriched
100Mo targets, which are significantly more expensive than natural isotopic targets and typically require recycling of the material, which can be costly, time consuming, and arduous.
Technetium-99m generators
Technetium-99m's short half-life of 6 hours makes storage impossible and would make transport very expensive. 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 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 the
99mTc 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 excited state of
99mTc. A
electron and a
electron antineutrino
The electron neutrino () is an elementary particle which has zero electric charge and a spin of . Together with the electron, it forms the first generation of leptons, hence the name electron neutrino. It was first hypothesized by Wolfgang Pauli ...
are emitted in the process (
99Mo →
99mTc + + ). The 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
Column chromatography in chemistry is a chromatography method used to isolate a single chemical compound from a mixture. Chromatography is able to separate substances based on differential adsorption of compounds to the adsorbent; compounds move th ...
, in which
99Mo in the form of water-soluble molybdate, MoO
42− is
adsorbed
Adsorption is the adhesion of atoms, ions or molecules from a gas, liquid or dissolved solid to a surface. This process creates a film of the ''adsorbate'' on the surface of the ''adsorbent''. This process differs from absorption, in which a ...
onto acid alumina (Al
2O
3). When the
99Mo decays, it forms
pertechnetate
The pertechnetate ion () is an oxyanion with the chemical formula . It is often used as a convenient water-soluble source of isotopes of the radioactive element technetium (Tc). In particular it is used to carry the 99mTc isotope (half-life 6 hou ...
TcO
4−, which, because of its single charge, is less tightly bound to the alumina. Pulling normal saline solution through the column of immobilized
99MoO
42− elutes the soluble
99mTcO
4−, 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.
Preparation
Technetium exits the generator in the form of the pertechnetate ion, TcO
4−. 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
99mTc, a
reducing agent is added to the pertechnetate solution to bring the oxidation state of the technecium 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
Radioisotope renography is a form of medical imaging of the kidneys that uses radiolabelling. A renogram, which may also be known as a MAG3 scan, allows a nuclear medicine physician or a radiologist to visualize the kidneys and learn more about how ...
to measure renal function.
[ Historical perspective, full text]
Medical uses
In 1970, Eckelman and Richards presented the first "kit" containing all the ingredients required to release the
99mTc, "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
A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a ve ...
, myocardium, thyroid, lungs, liver
The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...
, gallbladder
In vertebrates, the gallbladder, also known as the cholecyst, is a small hollow organ where bile is stored and concentrated before it is released into the small intestine. In humans, the pear-shaped gallbladder lies beneath the liver, although ...
, kidneys, skeleton, blood, and tumor
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
s. A more recent review is also available.
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
Radioisotope renography is a form of medical imaging of the kidneys that uses radiolabelling. A renogram, which may also be known as a MAG3 scan, allows a nuclear medicine physician or a radiologist to visualize the kidneys and learn more about how ...
.
Technetium-99m (Tc-99m) can be readily detected in the body by medical equipment because it emits 140.5 keV Kev can refer to:
Given name
* Kev Adams, French comedian, actor, screenwriter and film producer born Kevin Smadja in 1991
* Kevin Kev Carmody (born 1946), Indigenous Australian singer-songwriter
* Kev Coghlan (born 1988), Scottish Grand Prix moto ...
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). Besides, it emits no particle radiation, thus keeping radiation dosage low. Its decay product, 99Tc, has a relatively long half-life (211,000 years) and emits little radiation. The short physical half-life of 99mTc and its biological half-life
Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...
of 1 day with its other favourable properties allows scanning procedures to collect data rapidly and keep total patient radiation exposure low. Chemically, technetium is selectively concentrated in thyroid, salivary glands, and stomach and excluded from cerebrospinal fluid. Combination with perchlorate abolishes its selectiveness.
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 ( millicurie or mCi; and Mega-Becquerel
The becquerel (; symbol: Bq) is the unit of radioactivity in the International System of Units (SI). One becquerel is defined as the activity of a quantity of radioactive material in which one nucleus decays per second. For applications relatin ...
or MBq) for adults. These doses result in radiation exposures to the patient around 10 m Sv (1000 mrem), the equivalent of about 500 chest X-ray exposures. This level of radiation exposure is estimated by the linear no-threshold model
The linear no-threshold model (LNT) is a dose-response model used in radiation protection to estimate stochastic health effects such as radiation-induced cancer, genetic mutations and teratogenic effects on the human body due to exposure to io ...
to carry 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
Ionization, or Ionisation is the process by which an atom or a molecule acquires a negative or positive charge by gaining or losing electrons, often in conjunction with other chemical changes. The resulting electrically charged atom or molecul ...
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 with 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 99mTc. 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, 99mTc 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 99mTc 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 99mTc. 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 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 ) 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 when compared with 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 99mTc, the radiopharmaceuticals 99mTc- tetrofosmin (Myoview, GE Healthcare) or 99mTc- sestamibi (Cardiolite, Bristol-Myers Squibb
The Bristol Myers Squibb Company (BMS) is an American multinational pharmaceutical company. Headquartered in New York City, BMS is one of the world's largest pharmaceutical companies and consistently ranks on the ''Fortune'' 500 list of the lar ...
) are used. Following this, myocardial stress is induced, either by exercise or pharmacologically with adenosine, dobutamine
Dobutamine is a medication used in the treatment of cardiogenic shock (as a result of inadequate tissue perfusion) and severe heart failure. It may also be used in certain types of cardiac stress tests. It is given by IV only, as an injection in ...
or dipyridamole
Dipyridamole (trademarked as Persantine and others) is a nucleoside transport inhibitor and a PDE3 inhibitor medication that inhibits blood clot formation when given chronically and causes blood vessel dilation when given at high doses over a ...
(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
Cardiac ventriculography is a medical imaging test used to determine a person's heart function in the right, or left ventricle.Google books no page number Cardiac ventriculography involves injecting contrast media into the heart's ventricle(s) t ...
, 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
Valvular heart disease is any cardiovascular disease process involving one or more of the four valves of the heart (the aortic and mitral valves on the left side of heart and the pulmonic and tricuspid valves on the right side of heart). These ...
, congenital heart disease
A congenital heart defect (CHD), also known as a congenital heart anomaly and congenital heart disease, is a defect in the structure of the heart or great vessels that is present at birth. A congenital heart defect is classed as a cardiovascular ...
s, cardiomyopathy, and other cardiac disorder
Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, hea ...
s. As a nuclear stress test, the average radiation exposure is 9.4 mSv, which when compared with a typical 2 view chest X-ray (.1 mSv) is equivalent to 94 Chest X-Rays.[ It exposes patients to less radiation than comparable chest X-ray studies.][Merck manuals > Radionuclide Imaging]
Last full review/revision May 2009 by Michael J. Shea, MD. Content last modified May 2009
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
Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a r ...
or malignant melanoma
Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ...
. This is usually performed at the time of biopsy
A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a dise ...
or resection.99mTc-labelled filtered sulfur colloid or Technetium (99mTc) tilmanocept are 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 tracer that was previously injected around the biopsy site. An injection of Methylene blue or isosulfan blue is done at the same time to dye any draining nodes visibly blue. 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 lymph nodes blue that are draining from the area around the tumor.
Immunoscintigraphy
Immunoscintigraphy incorporates 99mTc into a monoclonal antibody
A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell.
Monoclonal antibodies ...
, an immune system protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
, capable of binding to cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
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
Sanofi S.A. is a French multinational pharmaceutical and healthcare company headquartered in Paris, France. Originally, the corporation was established in 1973 and merged with Synthélabo in 1999 to form Sanofi-Synthélabo. In 2004, Sanofi-Syn ...
) under the name "Scintium".
Blood pool labeling
When 99mTc is combined with a tin compound, it binds to red blood cell
Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...
s 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
In chemistry, pyrophosphates are phosphorus oxyanions that contain two phosphorus atoms in a P–O–P linkage. A number of pyrophosphate salts exist, such as disodium pyrophosphate (Na2H2P2O7) and tetrasodium pyrophosphate (Na4P2O7), among othe ...
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
The pertechnetate ion () is an oxyanion with the chemical formula . It is often used as a convenient water-soluble source of isotopes of the radioactive element technetium (Tc). In particular it is used to carry the 99mTc isotope (half-life 6 hou ...
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
A Meckel's diverticulum, a true congenital diverticulum, is a slight bulge in the small intestine present at birth and a vestigial remnant of the omphalomesenteric duct (also called the vitelline duct or yolk stalk). It is the most common malformat ...
with Meckel's Scans.
See also
* Cholescintigraphy
* Isotopes of technetium
* Transient equilibrium
Notes
References
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Further reading
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External links
99mTc production simulator – IAEA
{{DEFAULTSORT:Technetium-099m
Metastable isotopes
Medical physics
Radiopharmaceuticals
Radiochemistry
Medicinal radiochemistry