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Technetium-99m (99mTc) is a
metastable In chemistry and physics, metastability is 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 is onl ...
nuclear isomer A nuclear isomer is a metastable state of an atomic nucleus, in which one or more nucleons (protons or neutrons) occupy excited state levels (higher energy levels). "Metastable" describes nuclei whose excited states have Half-life, half-lives of ...
of
technetium-99 Technetium-99 (99Tc) is an isotope of technetium that 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; it has Symbol (chemistry), symbol Tc and atomic number 43. It is the lightest element whose isotopes are all radioactive. Technetium and promethium are the only radioactive elements whose neighbours in the sense ...
), 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 A radioactive tracer, radiotracer, or radioactive label is a synthetic derivative of a natural compound in which one or more atoms have been replaced by a radionuclide (a radioactive atom). By virtue of its radioactive decay, it can be used to ...
and can be detected in the body by medical equipment (
gamma camera A gamma camera (γ-camera), also called a scintillation camera or Anger camera, is a device used to image gamma radiation emitting radioisotopes, a technique known as scintigraphy. The applications of scintigraphy include early drug development ...
s). It is well suited to the role, because it emits readily detectable
gamma ray A gamma ray, also known as gamma radiation (symbol ), is a penetrating form of electromagnetic radiation arising from high energy interactions like the radioactive decay of atomic nuclei or astronomical events like solar flares. It consists o ...
s with a
photon energy Photon energy is the energy carried by a single photon. The amount of energy is directly proportional to the photon's electromagnetic frequency and thus, equivalently, is inversely proportional to the wavelength. The higher the photon's frequenc ...
of 140 
keV In physics, an electronvolt (symbol eV), also written electron-volt and electron volt, is the measure of an amount of kinetic energy gained by a single electron accelerating through an electric potential difference of one volt in vacuum. When us ...
(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 particles that can ...
s are about the same wavelength as emitted by conventional X-ray diagnostic equipment) and its
half-life Half-life is a mathematical and scientific description of exponential or gradual decay. Half-life, half life or halflife may also refer to: Film * Half-Life (film), ''Half-Life'' (film), a 2008 independent film by Jennifer Phang * ''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 Half-life is a mathematical and scientific description of exponential or gradual decay. Half-life, half life or halflife may also refer to: Film * Half-Life (film), ''Half-Life'' (film), a 2008 independent film by Jennifer Phang * ''Half Life: ...
of the isotope and its
biological half-life Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a drug, biological substance (such as a medication) to decrease from its maximum concentration (chemistry), concentration (Cmax (pharm ...
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 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: Januar ...
bombardment of
molybdenum Molybdenum is a chemical element; it has Symbol (chemistry), symbol Mo (from Neo-Latin ''molybdaenum'') and atomic number 42. The name derived from Ancient Greek ', meaning lead, since its ores were confused with lead ores. Molybdenum minerals hav ...
. This procedure produced
molybdenum-99 Molybdenum (42Mo) has 39 known isotopes, ranging in atomic mass from 81 to 119, 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 Enriched uranium is a type of uranium in which the percent composition of uranium-235 (written 235U) has been increased through the process of isotope separation. Naturally occurring uranium is composed of three major isotopes: uranium-238 (238 ...
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 nuclear physicist and radiochemist who discovered the elements technetium and astatine, and the antiproton, a subatomic antiparticle, for which he was award ...
and
Glenn T. Seaborg Glenn Theodore Seaborg ( ; April 19, 1912February 25, 1999) was an American chemist whose involvement in the synthesis, discovery and investigation of ten transuranium elements earned him a share of the 1951 Nobel Prize in Chemistry. His work i ...
isolated for the first time the
metastable isotope A nuclear isomer is a metastable state of an atomic nucleus, in which one or more nucleons (protons or neutrons) occupy excited state levels (higher energy levels). "Metastable" describes nuclei whose excited states have half-lives of 10−9 seco ...
technetium-99m, after bombarding natural molybdenum with 8 MeV
deuteron Deuterium (hydrogen-2, symbol H or D, also known as heavy hydrogen) is one of two Stable isotope ratio, stable isotopes of hydrogen; the other is protium, or hydrogen-1, H. The deuterium atomic nucleus, nucleus (deuteron) contains one proton and ...
s in the
cyclotron A cyclotron is a type of particle accelerator invented by Ernest 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: Januar ...
of
Ernest Orlando Lawrence Ernest Orlando Lawrence (August 8, 1901 – August 27, 1958) was an American accelerator physicist who received the Nobel Prize in Physics in 1939 for his invention of the cyclotron. He is known for his work on uranium-isotope separation for ...
's
Radiation laboratory The Radiation Laboratory, commonly called the Rad Lab, was a microwave and radar research laboratory located at the Massachusetts Institute of Technology (MIT) in Cambridge, Massachusetts. It was first created in October 1940 and operated until 3 ...
. In 1970 Seaborg explained that: Later in 1940, Emilio Segrè and
Chien-Shiung Wu Chien-Shiung Wu ( zh, t=吳健雄, p=Wú Jiànxióng, w=Wu2 Chien4-Hsiung2; May 31, 1912 – February 16, 1997) was a Chinese-American particle physics, particle and experimental physicist who made significant contributions in the fields of nucle ...
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 Powell may refer to: People * Powell (surname) * Powell (given name) * Powell baronets, several baronetcies * Colonel Powell (disambiguation), several military officers * General Powell (disambiguation), several military leaders * Governor Powell ...
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 laboratories, United States Department of Energy national laboratory located in Upton, New York, a hamlet of the Brookhaven, New York, Town of Brookhaven. It w ...
, 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: washing of loaded ion-exchange resins to remove captured ions, or eluting proteins or other biopolymers from an el ...
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 There are 39 known isotopes and 17 nuclear isomers of tellurium (52Te), with atomic masses that range from 104 to 142. These are listed in the table below. Naturally-occurring tellurium on Earth consists of eight isotopes. Two of these have been ...
(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 A technetium-99m generator, or colloquially a technetium cow or moly cow, is a device used to extract the metastable isotope 99mTc of technetium from a decaying sample of molybdenum-99. 99Mo has a half-life of 66 hours and can be easily tran ...
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 camera A gamma camera (γ-camera), also called a scintillation camera or Anger camera, is a device used to image gamma radiation emitting radioisotopes, a technique known as scintigraphy. The applications of scintigraphy include early drug development ...
s.


Americas

Between 1963 and 1966, numerous scientific studies demonstrated the use of 99mTc as
radiotracer A radioactive tracer, radiotracer, or radioactive label is a synthetic derivative of a natural compound in which one or more atoms have been replaced by a radionuclide (a radioactive atom). By virtue of its radioactive decay, it can be used to ...
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 laboratories, United States Department of Energy national laboratory located in Upton, New York, a hamlet of the Brookhaven, New York, Town of Brookhaven. It w ...
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 Union Carbide Corporation (UCC) is an American chemical company headquartered in Seadrift, Texas. It has been a wholly owned subsidiary of Dow Chemical Company since 2001. Union Carbide produces chemicals and polymers that undergo one or more f ...
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 Nuclear fission products are the atomic fragments left after a large atomic nucleus undergoes nuclear fission. Typically, a large nucleus like that of uranium fissions by splitting into two smaller nuclei, along with a few neutrons, the releas ...
that resulted from the irradiation of
highly enriched uranium Enriched uranium is a type of uranium in which the percent composition of uranium-235 (written 235U) has been increased through the process of isotope separation. Naturally occurring uranium is composed of three major isotopes: uranium-238 (238 ...
(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 UO2 on the inside of a cylindrical target. At the end of the 1970s, of total fission product radiation were extracted weekly from 20 to 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 Chalk River Laboratories (; also known as CRL, Chalk River Labs and formerly Chalk River Nuclear Laboratories, CRNL) is a Canadian nuclear research facility in Deep River, about north-west of Ottawa. CRL is a site of significant research and ...
, 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 Argentina, officially the Argentine Republic, is a country in the southern half of South America. It covers an area of , making it the List of South American countries by area, second-largest country in South America after Brazil, the fourt ...
in 1967, with 99Mo produced in the CNEA's
RA-1 Enrico Fermi RA-1 Enrico Fermi is a research reactor in Argentina. It was the first nuclear reactor to be built in that country and the first research reactor in the southern hemisphere. Construction started in April 1957, with first criticality on 20 January ...
reactor. Besides its domestic market CNEA supplies 99Mo to some South American countries.


Oceania

In 1967, the first 99mTc procedures were carried out in
Auckland Auckland ( ; ) is a large metropolitan city in the North Island of New Zealand. It has an urban population of about It is located in the greater Auckland Region, the area governed by Auckland Council, which includes outlying rural areas and ...
,
New Zealand New Zealand () is an island country in the southwestern Pacific Ocean. It consists of two main landmasses—the North Island () and the South Island ()—and List of islands of New Zealand, over 600 smaller islands. It is the List of isla ...
. 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 that is responsible for nuclear research and the production of radioisotopes for nuclear medicine. It was established in Apr ...
) 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 Covidien plc was an Irish-headquartered global health care products company and manufacturer of medical devices and supplies. Covidien became an independent publicly traded company after being spun off from Tyco International in 2007. It was pu ...
) 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, Énergie atomique du Canada limitée, EACL) is a Canadian Crown corporation and the largest nuclear science and technology laboratory in Canada. AECL developed the CANDU reactor technology starting in th ...
announced the detection of a small leak of
heavy water Heavy water (deuterium oxide, , ) is a form of water (molecule), water in which hydrogen atoms are all deuterium ( or D, also known as ''heavy hydrogen'') rather than the common hydrogen-1 isotope (, also called ''protium'') that makes up most o ...
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 Columbia is a city in Missouri, United States. It was founded in 1821 as the county seat of Boone County, Missouri, Boone County and had a population of 126,254 as recorded in the 2020 United States census, making it the List of cities in Misso ...
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 excited state levels (higher energy levels). "Metastable" describes nuclei whose excited states have Half-life, half-lives of ...
, as indicated by the "m" after its
mass number The mass number (symbol ''A'', from the German word: ''Atomgewicht'', "atomic 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 appro ...
99. This means it is a nuclide in an excited (metastable) state that lasts much longer than is typical. The nucleus will eventually relax (i.e., de-excite) to its
ground state The ground state of a quantum-mechanical system is its stationary state of lowest energy; the energy of the ground state is known as the zero-point energy of the system. An excited state is any state with energy greater than the ground state ...
through the emission of
gamma ray A gamma ray, also known as gamma radiation (symbol ), is a penetrating form of electromagnetic radiation arising from high energy interactions like the radioactive decay of atomic nuclei or astronomical events like solar flares. It consists o ...
s 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. Until the 1960s, nucleons were thought to be ele ...
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 A radioactive tracer, radiotracer, or radioactive label is a synthetic derivative of a natural compound in which one or more atoms have been replaced by a radionuclide (a radioactive atom). By virtue of its radioactive decay, it can be used to ...
for
medical imaging Medical imaging is the technique and process of imaging the interior of a body for clinical analysis and medical intervention, as well as visual representation of the function of some organs or tissues (physiology). Medical imaging seeks to revea ...
. The remaining approximately 12% of 99mTc decays are by means of
internal conversion Internal conversion is an 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 conversion (o ...
, 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 i ...
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, known as beta decay. There are two forms of beta decay, β− decay and � ...
electrons would do, contributing along with the 140.5 keV and 142.6 keV gammas to the total deposited
dose Dose or Dosage may refer to: Music * ''Dose'' (Gov't Mule album), 1998 * ''Dose'' (Latin Playboys album) * ''Dosage'' (album), by the band Collective Soul * "Dose" (song), a 2018 song by Ciara * "Dose", song by Filter from the album '' Short ...
. Pure gamma emission is the desirable
decay mode Radioactive decay (also known as nuclear decay, radioactivity, radioactive disintegration, or nuclear disintegration) is the process by which an unstable atomic nucleus loses energy by radiation. A material containing unstable nuclei is conside ...
for medical imaging because other particles deposit more energy in the patient body (
radiation dose Ionizing (ionising) radiation, including nuclear radiation, consists of subatomic particles or electromagnetic waves that have enough energy per individual photon or particle to ionize atoms or molecules by detaching electrons from them. Some pa ...
) than in the camera. Metastable isomeric transition is the only nuclear decay mode that approaches pure gamma emission. 99mTc's
half-life Half-life is a mathematical and scientific description of exponential or gradual decay. Half-life, half life or halflife may also refer to: Film * Half-Life (film), ''Half-Life'' (film), a 2008 independent film by Jennifer Phang * ''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 Radioactive decay (also known as nuclear decay, radioactivity, radioactive disintegration, or nuclear disintegration) is the process by which an unstable atomic nucleus loses energy by radiation. A material containing unstable nuclei is conside ...
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 Medical imaging is the technique and process of imaging the interior of a body for clinical analysis and medical intervention, as well as visual representation of the function of some organs or tissues (physiology). Medical imaging seeks to revea ...
. After gamma emission or internal conversion, the resulting ground-state technetium-99 then decays with a half-life of 211,000 years to
stable A stable is a building in which working animals are kept, especially horses or oxen. The building is usually divided into stalls, and may include storage for equipment and feed. Styles There are many different types of stables in use tod ...
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 -> ce 11,000\ \ce\overbrace^


Production


Production of 99Mo in nuclear reactors


Neutron irradiation of uranium-235 targets

The parent nuclide of 99mTc, 99Mo, is mainly extracted for medical purposes from the
fission product Nuclear fission products are the atomic fragments left after a large atomic nucleus undergoes nuclear fission. Typically, a large nucleus like that of uranium fissions by splitting into two smaller nuclei, along with a few neutrons, the releas ...
s created in neutron-irradiated
uranium-235 Uranium-235 ( or U-235) is an isotope of uranium making up about 0.72% of natural uranium. Unlike the predominant isotope uranium-238, it is fissile, i.e., it can sustain a nuclear chain reaction. It is the only fissile isotope that exists in nat ...
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 maritim ...
s around the world using
highly enriched uranium Enriched uranium is a type of uranium in which the percent composition of uranium-235 (written 235U) has been increased through the process of isotope separation. Naturally occurring uranium is composed of three major isotopes: uranium-238 (238 ...
(HEU) targets. Smaller amounts of 99Mo are produced from
low-enriched uranium Enriched uranium is a type of uranium in which the percent composition of uranium-235 (written 235U) has been increased through the process of isotope separation. Naturally occurring uranium is composed of three major isotopes: uranium-238 (238U ...
in at least three reactors.


Neutron activation of 98Mo

Production of 99Mo by
neutron activation Neutron activation is the process in which neutron radiation induces radioactivity in materials, and occurs when atomic nuclei capture free neutrons, becoming heavier and entering excited states. The excited nucleus decays immediately by emi ...
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 Advanced Cyclotron Systems, Inc. (ACSI) is a company based in Richmond, British Columbia, Canada that supplies and services cyclotrons predominantly used for the production of medical isotopes by hospitals for nuclear medicine. The company was a ...
, for 99mTc production at the
University of Alberta The University of Alberta (also known as U of A or UAlberta, ) is a public research university located in Edmonton, Alberta, Canada. It was founded in 1908 by Alexander Cameron Rutherford, the first premier of Alberta, and Henry Marshall Tory, t ...
and the
Université de Sherbrooke The Université de Sherbrooke (UdeS; Quebec English, English: ''University of Sherbrooke'') is a French-language Public university, public research university in Sherbrooke, Quebec, Canada, with a second campus in Longueuil, a suburb on the Mont ...
, and is planning others at the
University of British Columbia The University of British Columbia (UBC) is a Public university, public research university with campuses near University of British Columbia Vancouver, Vancouver and University of British Columbia Okanagan, Kelowna, in British Columbia, Canada ...
,
TRIUMF Triumf may refer to: * TRIUMF, Canada's national particle accelerator centre * 14959 TRIUMF, a minor planet * S-400 Triumf, a Russian anti-aircraft weapon system developed in the 1990s * Triumf Riza (1979–2007), Kosovo police officer and member o ...
,
University of Saskatchewan The University of Saskatchewan (U of S, or USask) is a Universities in Canada, Canadian public university, public research university, founded on March 19, 1907, and located on the east side of the South Saskatchewan River in Saskatoon, Saskatch ...
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 generator A technetium-99m generator, or colloquially a technetium cow or moly cow, is a device used to extract the metastable isotope 99mTc of technetium from a decaying sample of molybdenum-99. 99Mo has a half-life of 66 hours and can be easily tran ...
s 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 Radiation Dosages Recognized effects of higher acute radiation doses are described in more detail in the article on radiation poisoning. Although the International System of Units (SI) defines the sievert (Sv) as the unit of radiation dose equ ...
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 In nuclear physics, beta decay (β-decay) is a type of radioactive decay in which an atomic nucleus emits a beta particle (fast energetic electron or positron), transforming into an isobar of that nuclide. For example, beta decay of a neutron ...
. Over 87% of the decays lead to the excited state of 99mTc. A
electron The electron (, or in nuclear reactions) is a subatomic particle with a negative one elementary charge, elementary electric charge. It is a fundamental particle that comprises the ordinary matter that makes up the universe, along with up qua ...
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 ...
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 In particle physics, bremsstrahlung (; ; ) is electromagnetic radiation produced by the deceleration of a charged particle when deflected by another charged particle, typically an electron by an atomic nucleus. The moving particle loses kinetic ...
''). 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 compounds, chemical compound from a mixture. Chromatography is able to separate substances based on differential absorption of compounds to the adsorbe ...
, in which 99Mo in the form of water-soluble molybdate, MoO42− 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 f ...
onto acid alumina (Al2O3). 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 Technetium-99m, 99mTc isotope ( ...
TcO4, which, because of its single charge, is less tightly bound to the alumina. Pulling normal saline solution through the column of immobilized 99MoO42−
elute In analytical and organic chemistry, elution is the process of extracting one material from another by washing with a solvent: washing of loaded ion-exchange resins to remove captured ions, or eluting proteins or other biopolymers from an elec ...
s 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.


Preparation

Technetium exits the generator in the form of the pertechnetate ion, TcO4. The
oxidation state In chemistry, the oxidation state, or oxidation number, is the hypothetical Electrical charge, charge of an atom if all of its Chemical bond, bonds to other atoms are fully Ionic bond, ionic. It describes the degree of oxidation (loss of electrons ...
of Tc in this compound is +7. This is directly suitable for medical applications only in
bone scan A bone scan or bone scintigraphy is a nuclear medicine imaging technique used to help diagnose and assess different bone diseases. These include cancer of the bone or metastasis, location of bone inflammation and fractures (that may not be vis ...
s (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 In chemistry, a reducing agent (also known as a reductant, reducer, or electron donor) is a chemical species that "donates" an electron to an (called the , , , or ). Examples of substances that are common reducing agents include hydrogen, carbon ...
is added to the pertechnetate solution to bring the oxidation state of the technecium down to +3 or +4. Secondly, a
ligand In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's el ...
is added to form a
coordination complex A coordination complex is a chemical compound consisting of a central atom or ion, which is usually metallic and is called the ''coordination centre'', and a surrounding array of chemical bond, bound molecules or ions, that are in turn known as ' ...
. The ligand is chosen to have an affinity for the specific organ to be targeted. For example, the
exametazime Technetium (99mTc) exametazime is a radiopharmaceutical sold under the trade name Ceretec, and is used by nuclear medicine physicians for the detection of altered regional cerebral perfusion in stroke and other cerebrovascular diseases. It can a ...
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. 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 A radioactive tracer, radiotracer, or radioactive label is a synthetic derivative of a natural compound in which one or more atoms have been replaced by a radionuclide (a radioactive atom). By virtue of its radioactive decay, it can be used to ...
. Klaus Schwochau's book ''Technetium'' lists 31
radiopharmaceuticals 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 ...
based on 99mTc for imaging and functional studies of the
brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...
,
myocardium Cardiac muscle (also called heart muscle or myocardium) is one of three types of vertebrate muscle tissues, the others being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that constitutes the main tissue of the wall o ...
,
thyroid The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans, it is a butterfly-shaped gland located in the neck below the Adam's apple. It consists of two connected lobes. The lower two thirds of the lobes are connected by ...
,
lung The lungs are the primary Organ (biology), organs of the respiratory system in many animals, including humans. In mammals and most other tetrapods, two lungs are located near the Vertebral column, backbone on either side of the heart. Their ...
s,
liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
,
gallbladder In vertebrates, the gallbladder, also known as the cholecyst, is a small hollow Organ (anatomy), organ where bile is stored and concentrated before it is released into the small intestine. In humans, the pear-shaped gallbladder lies beneath t ...
,
kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...
s,
skeleton A skeleton is the structural frame that supports the body of most animals. There are several types of skeletons, including the exoskeleton, which is a rigid outer shell that holds up an organism's shape; the endoskeleton, a rigid internal fra ...
,
blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood is com ...
, 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 Technetium (99mTc) exametazime is a radiopharmaceutical sold under the trade name Ceretec, and is used by nuclear medicine physicians for the detection of altered regional cerebral perfusion in stroke and other cerebrovascular diseases. It can a ...
(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 Assessment of kidney function occurs in different ways, using the presence of symptoms and signs, as well as measurements using urine tests, blood tests, and medical imaging. Functions of a healthy kidney include maintaining a person's flu ...
is done by attaching 99mTc to mercaptoacetyl triglycine ( MAG3); this procedure is known as a MAG3 scan. Technetium-99m (Tc-99m) can be readily detected in the body by medical equipment because it emits 140.5
keV In physics, an electronvolt (symbol eV), also written electron-volt and electron volt, is the measure of an amount of kinetic energy gained by a single electron accelerating through an electric potential difference of one volt in vacuum. When us ...
gamma ray A gamma ray, also known as gamma radiation (symbol ), is a penetrating form of electromagnetic radiation arising from high energy interactions like the radioactive decay of atomic nuclei or astronomical events like solar flares. It consists o ...
s (these are about the same wavelength as emitted by conventional X-ray diagnostic equipment), and its
half-life Half-life is a mathematical and scientific description of exponential or gradual decay. Half-life, half life or halflife may also refer to: Film * Half-Life (film), ''Half-Life'' (film), a 2008 independent film by Jennifer Phang * ''Half Life: ...
for gamma emission is six hours (meaning 94% of it decays to 99Tc in 24 hours). Besides, it emits virtually no beta 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 Half-life is a mathematical and scientific description of exponential or gradual decay. Half-life, half life or halflife may also refer to: Film * Half-Life (film), ''Half-Life'' (film), a 2008 independent film by Jennifer Phang * ''Half Life: ...
of 99mTc and its
biological half-life Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a drug, biological substance (such as a medication) to decrease from its maximum concentration (chemistry), concentration (Cmax (pharm ...
of 1 day with its other favourable properties allows scanning procedures to collect data rapidly and keep total patient radiation exposure low. Chemically, technetium-99m is selectively concentrated in the stomach, thyroid, and salivary glands, and excluded from
cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless Extracellular fluid#Transcellular fluid, transcellular body fluid found within the meninges, meningeal tissue that surrounds the vertebrate brain and spinal cord, and in the ventricular system, ven ...
; combining it 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 Single-photon emission computed tomography (SPECT, or less commonly, SPET) is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera (that is, ...
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 an activity of one per second, on average, for aperiodic activity events referred to a radionuclide. For applicatio ...
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 A chest radiograph, chest X-ray (CXR), or chest film is a Projectional radiography, projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures. Chest radiographs are the most common fi ...
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 Electric charge, charge by gaining or losing electrons, often in conjunction with other chemical changes. The resulting electrically charged at ...
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 A computed tomography scan (CT scan), formerly called computed axial tomography scan (CAT scan), is a medical imaging technique used to obtain detailed internal images of the body. The personnel that perform CT scans are called radiographers or ...
. 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 Single-photon emission computed tomography (SPECT, or less commonly, SPET) is a nuclear medicine tomography, tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera ...
(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 A gamma camera (γ-camera), also called a scintillation camera or Anger camera, is a device used to image gamma radiation emitting radioisotopes, a technique known as scintigraphy. The applications of scintigraphy include early drug development ...
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 scan A bone scan or bone scintigraphy is a nuclear medicine imaging technique used to help diagnose and assess different bone diseases. These include cancer of the bone or metastasis, location of bone inflammation and fractures (that may not be vis ...
s, 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 Nuclear medicine (nuclear radiology, nucleology), is a medical specialty involving the application of radioactivity, radioactive substances in the diagnosis and treatment of disease. Nuclear imaging is, in a sense, ''radiology done inside out'', ...
technique commonly called the
bone scan A bone scan or bone scintigraphy is a nuclear medicine imaging technique used to help diagnose and assess different bone diseases. These include cancer of the bone or metastasis, location of bone inflammation and fractures (that may not be vis ...
usually uses 99mTc. It is not to be confused with the "bone density scan",
DEXA Dual-energy X-ray absorptiometry (DXA, or DEXA) is a means of measuring bone mineral density (BMD) with spectral imaging. Two X-ray beams, with different energy levels, are aimed at the patient's bones. When soft tissue absorption is subtracted, ...
, 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 Osteoblasts (from the Greek combining forms for " bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cells with a single nucleus that synthesize bone. However, in the process of bone formation, osteoblasts fu ...
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 A gamma camera (γ-camera), also called a scintillation camera or Anger camera, is a device used to image gamma radiation emitting radioisotopes, a technique known as scintigraphy. The applications of scintigraphy include early drug development ...
. Medronic acid is a
phosphate Phosphates are the naturally occurring form of the element phosphorus. In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthop ...
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 Single-photon emission computed tomography (SPECT, or less commonly, SPET) is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera (that is, ...
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 Coronary artery disease (CAD), also called coronary heart disease (CHD), or ischemic heart disease (IHD), is a type of heart disease involving the reduction of blood flow to the cardiac muscle due to a build-up of atheromatous plaque in the ...
. The underlying principle is, under conditions of stress, diseased
myocardium Cardiac muscle (also called heart muscle or myocardium) is one of three types of vertebrate muscle tissues, the others being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that constitutes the main tissue of the wall o ...
receives less blood flow than normal myocardium. MPI is one of several types of
cardiac stress test A cardiac stress test is a cardiological examination that evaluates the cardiovascular system's response to external stress within a controlled clinical setting. This stress response can be induced through physical exercise (usually a treadmill) o ...
. As a
nuclear stress test A cardiac stress test is a cardiological examination that evaluates the cardiovascular system's response to external stress within a controlled clinical setting. This stress response can be induced through physical exercise (usually a treadmill) o ...
, 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 Technetium (99mTc) tetrofosmin is a drug used in nuclear medicine cardiac imaging. It is sold under the brand name Myoview ( GE Healthcare). The radioisotope, technetium-99m, is chelated by two 1,2-''bis'' i-(2-ethoxyethyl)phosphinothane ligands ...
(Myoview, GE Healthcare) or 99mTc- sestamibi (Cardiolite,
Bristol-Myers Squibb The Bristol-Myers Squibb Company, doing business as Bristol Myers Squibb (BMS), is an American multinational pharmaceutical company. Headquartered in Princeton, New Jersey, BMS is one of the world's largest pharmaceutical companies and consist ...
) are used. Following this, myocardial stress is induced, either by exercise or pharmacologically with
adenosine Adenosine (symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9- glycosidic bond. Adenosine is one of the four nucleoside build ...
,
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 ...
or
dipyridamole Dipyridamole, sold under the brand name Persantine among others, is an antiplatelet drug of the nucleoside transport inhibitor and PDE3 inhibitor class that inhibits blood clot formation when given chronically and causes blood vessel dilatio ...
(Persantine), which increase the heart rate or by regadenoson(Lexiscan), a vasodilator. (
Aminophylline Aminophylline is a compound of the bronchodilator theophylline with ethylenediamine in 2:1 ratio. The ethylenediamine improves solubility, and the aminophylline is usually found as a dihydrate. Aminophylline is less potent and shorter-acting tha ...
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 Coronary artery disease (CAD), also called coronary heart disease (CHD), or ischemic heart disease (IHD), is a type of cardiovascular disease, heart disease involving Ischemia, the reduction of blood flow to the cardiac muscle due to a build-up ...
,
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). The ...
,
congenital heart disease A congenital heart defect (CHD), also known as a congenital heart anomaly, congenital cardiovascular malformation, and congenital heart disease, is a defect in the structure of the heart or great vessels that is present at birth. A congenital he ...
s,
cardiomyopathy Cardiomyopathy is a group of primary diseases of the heart muscle. Early on there may be few or no symptoms. As the disease worsens, shortness of breath, feeling tired, and swelling of the legs may occur, due to the onset of heart failure. A ...
, and other
cardiac disorder Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina, heart attack), heart failure, hypertensive heart disease, rheumatic he ...
s. As a
nuclear stress test A cardiac stress test is a cardiological examination that evaluates the cardiovascular system's response to external stress within a controlled clinical setting. This stress response can be induced through physical exercise (usually a treadmill) o ...
, 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 A chest radiograph, chest X-ray (CXR), or chest film is a Projectional radiography, projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures. Chest radiographs are the most common fi ...
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 Technetium (99mTc) exametazime is a radiopharmaceutical sold under the trade name Ceretec, and is used by nuclear medicine physicians for the detection of altered regional cerebral perfusion in stroke and other cerebrovascular diseases. It can a ...
). 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 Dementia is a syndrome associated with many neurodegenerative diseases, characterized by a general decline in cognitive abilities that affects a person's ability to perform activities of daily living, everyday activities. This typically invo ...
. When used with the 3-D
SPECT Single-photon emission computed tomography (SPECT, or less commonly, SPET) is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera (that is, ...
technique, they compete with brain
FDG-PET Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, re ...
scans and
fMRI Functional magnetic resonance imaging or functional MRI (fMRI) measures brain activity by detecting changes associated with blood flow. This technique relies on the fact that cerebral blood flow and neuronal activation are coupled. When an area o ...
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 A lymph node, or lymph gland, is a kidney-shaped Organ (anatomy), organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphoc ...
draining a cancer, such as
breast cancer Breast cancer is a cancer that develops from breast tissue. Signs of breast cancer may include a Breast lump, lump in the breast, a change in breast shape, dimpling of the skin, Milk-rejection sign, milk rejection, fluid coming from the nipp ...
or
malignant melanoma Melanoma is the most dangerous type of skin cancer; it develops from the melanin-producing cells known as melanocytes. It typically occurs in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In very rare case ...
. This is usually performed at the time of
biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, an interventional radiologist, or an interventional cardiology, interventional cardiologist. The process involves the extraction of sampling (medicine), sample ...
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 Methylthioninium chloride, commonly called methylene blue, is a salt used as a dye and as a medication. As a medication, it is mainly used to treat methemoglobinemia. It has previously been used for treating cyanide poisoning and urinary trac ...
or
isosulfan blue Isosulfan blue, sold under the brand name Lymphazurin among others, is a contrast agent medication used to delineate the lymphatic vessels during a lymphography procedure. References External links

* * * Radiocontrast agents ...
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 antibodie ...
, an
immune system The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
, capable of binding to
cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
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
intestine The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascular system. T ...
s. 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. The corporation was established in 1973 and merged with Synthélabo in 1999 to form Sanofi-Synthélabo. In 2004, Sanofi-Synthélabo merg ...
) under the name Scintimun.


Blood pool labeling

When 99mTc is combined with a
tin Tin is a chemical element; it has symbol Sn () and atomic number 50. A silvery-colored metal, tin is soft enough to be cut with little force, and a bar of tin can be bent by hand with little effort. When bent, a bar of tin makes a sound, the ...
compound, it binds to
red blood cell Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood cel ...
s and can therefore be used to map
circulatory system In vertebrates, the circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the body. It includes the cardiovascular system, or vascular system, that consists of the heart ...
disorders. It is commonly used to detect gastrointestinal bleeding sites as well as
ejection fraction An ejection fraction (EF) is the volumetric fraction (or portion of the total) of fluid (usually blood) ejected from a chamber (usually the heart) with each contraction (or heartbeat). It can refer to the cardiac atrium, cardiac ventricle, gall ...
, 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 linkage. A number of pyrophosphate salts exist, such as disodium pyrophosphate () and tetrasodium pyrophosphate (), among others. Often pyrophosphates a ...
ion with 99mTc adheres to
calcium Calcium is a chemical element; it has symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to it ...
deposits in damaged
heart The heart is a muscular Organ (biology), organ found in humans and other animals. This organ pumps blood through the blood vessels. The heart and blood vessels together make the circulatory system. The pumped blood carries oxygen and nutrie ...
muscle, making it useful to gauge damage after a
heart attack A myocardial infarction (MI), commonly known as a heart attack, occurs when Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...
.


Sulfur colloid for spleen scan

The
sulfur Sulfur ( American spelling and the preferred IUPAC name) or sulphur ( Commonwealth spelling) is a chemical element; it has symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms ...
colloid of 99mTc is scavenged by the
spleen The spleen (, from Ancient Greek '' σπλήν'', splḗn) is an organ (biology), organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The spleen plays important roles in reg ...
, 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 Technetium-99m, 99mTc isotope ( ...
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 vitelline duct. It is the most common malformation of the Human gastrointestinal tract, gastrointesti ...
with Meckel's Scans.


Pulmonary

Carbon inhalation aerosol labeled with technetium-99m (Technegas) is
indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...
for the visualization of pulmonary ventilation and the evaluation of pulmonary embolism.


See also

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Cholescintigraphy Cholescintigraphy or hepatobiliary scintigraphy is scintigraphy of the hepatobiliary tract, including the gallbladder and bile ducts. The image produced by this type of medical imaging, called a cholescintigram, is also known by other names depe ...
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Isotopes of technetium Isotopes are distinct nuclear species (or '' nuclides'') of the same chemical element. They have the same atomic number (number of protons in their nuclei) and position in the periodic table (and hence belong to the same chemical element), b ...
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Transient equilibrium In nuclear physics, transient equilibrium is a situation in which equilibrium is reached by a parent-daughter radioactive isotope pair where the half-life of the daughter is shorter than the half-life of the parent. Contrary to secular equilibrium, ...


Notes


References

;Citations ;Bibliography * * * * * * *


Further reading

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External links


99mTc production simulator – IAEA
{{DEFAULTSORT:Technetium-099m Metastable isotopes Medical physics Radiochemistry Medicinal radiochemistry Medical isotopes