Tc-99m Decay Scheme
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Technetium-99m (99mTc) is a
metastable In chemistry and physics, metastability denotes an intermediate Energy level, energetic state within a dynamical system other than the system's ground state, state of least energy. A ball resting in a hollow on a slope is a simple example of me ...
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, higher energy levels than in the ground state of the same nucleus. "Metastable" describes nuclei whose excited ...
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, produc ...
(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 Radiopharmacology is radiochemistry applied to medicine and thus the pharmacology of radiopharmaceuticals (medicinal radiocompounds, that is, pharmaceutical drugs that are radioactive). Radiopharmaceuticals are used in the field of nuclear medic ...
in the world. Technetium-99m is used as a
radioactive tracer A radioactive tracer, radiotracer, or radioactive label is a chemical compound in which one or more atoms have been replaced by a radionuclide so by virtue of its radioactive decay it can be used to explore the mechanism of chemical reactions by ...
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 γ or \gamma), is a penetrating form of electromagnetic radiation arising from the radioactive decay of atomic nuclei. It consists of the shortest wavelength electromagnetic waves, typically ...
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 frequency, ...
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 motor ...
(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 always ...
s are about the same wavelength as emitted by conventional X-ray diagnostic equipment) and its
half-life Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable ato ...
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 (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable ato ...
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: Janu ...
bombardment of
molybdenum Molybdenum is a chemical element with the symbol Mo and atomic number 42 which is located in period 5 and group 6. The name is from Neo-Latin ''molybdaenum'', which is based on Ancient Greek ', meaning lead, since its ores were confused with lea ...
. 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 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 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 Nobel ...
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 in ...
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, higher energy levels than in the ground state of the same nucleus. "Metastable" describes nuclei whose excited ...
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: Janu ...
of
Ernest Orlando Lawrence Ernest Orlando Lawrence (August 8, 1901 – August 27, 1958) was an American Nuclear physics, nuclear physicist and winner of the Nobel Prize in Physics in 1939 for his invention of the cyclotron. He is known for his work on Enriched uran ...
'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 31 ...
. In 1970 Seaborg explained that: Later in 1940, Emilio Segrè and
Chien-Shiung Wu ) , spouse = , residence = , nationality = ChineseAmerican , field = Physics , work_institutions = Institute of Physics, Academia SinicaUniversity of California at BerkeleySmith CollegePrinceton UniversityColumbia UniversityZhejiang Unive ...
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 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 Margaret is a female first name, derived via French () and Latin () from grc, μαργαρίτης () meaning "pearl". The Greek is borrowed from Persian. Margaret has been an English name since the 11th century, and remained popular througho ...
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 exa ...
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 ( ...
iodine-132 There are 37 known isotopes of iodine (53I) from 108I to 144I; all undergo radioactive decay except 127I, which is stable. Iodine is thus a monoisotopic element. Its longest-lived radioactive isotope, 129I, has a half-life of 15.7 million yea ...
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 transpo ...
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 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 Union Carbide Corporation is an American chemical corporation wholly owned subsidiary (since February 6, 2001) by Dow Chemical Company. Union Carbide produces chemicals and polymers that undergo one or more further conversions by customers befor ...
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 release ...
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 (238U ...
(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 20-30 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 The Multipurpose Applied Physics Lattice Experiment (MAPLE), later renamed MDS Medical Isotope Reactors (MMIR), was a dedicated isotope-production facility built by AECL and MDS Nordion. It was intended to include two identical reactors, as well ...
(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 (french: Laboratoires de Chalk River; 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 ...
, 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 ( es, link=no, República Argentina), is a country in the southern half of South America. Argentina covers an area of , making it the second-largest country in South America after Brazil, th ...
in 1967, with 99Mo produced in the
CNEA The National Atomic Energy Commission ( es, Comisión Nacional de Energía Atómica, CNEA) is the Argentine government agency in charge of nuclear energy research and development. The agency was created on May 31, 1950, with the mission of deve ...
'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 List of New Zealand urban areas by population, most populous urban area in the country and the List of cities in Oceania by po ...
,
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 Covidien 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 purcha ...
) 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 thi ...
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 Columbia is a city in the U.S. state of Missouri. It is the county seat of Boone County and home to the University of Missouri. Founded in 1821, it is the principal city of the five-county Columbia metropolitan area. It is Missouri's fourth ...
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, higher energy levels than in the ground state of the same nucleus. "Metastable" describes nuclei whose excited ...
, 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 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 ( ...
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 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 γ or \gamma), is a penetrating form of electromagnetic radiation arising from the radioactive decay of atomic nuclei. It consists of the shortest wavelength electromagnetic waves, typically ...
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 (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 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 ...
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 rev ...
. 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 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 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 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 consid ...
for medical imaging because other particles deposit more energy in the patient body (
radiation dose Ionizing radiation (or ionising radiation), including nuclear radiation, consists of subatomic particles or electromagnetic waves that have sufficient energy to ionize atoms or molecules by detaching electrons from them. Some particles can travel ...
) than in the camera. Metastable isomeric transition is the only nuclear decay mode that approaches pure gamma emission. 99mTc's
half-life Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable ato ...
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 consid ...
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 is ...
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 rev ...
. 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 livestock, especially horses, are kept. It most commonly means a building that is divided into separate stalls for individual animals and livestock. There are many different types of stables in use today; the ...
ruthenium-99 Naturally occurring ruthenium (44Ru) is composed of seven stable isotopes. Additionally, 27 radioactive isotopes have been discovered. Of these radioisotopes, the most stable are 106Ru, with a half-life of 373.59 days; 103Ru, with a half-life of 3 ...
. 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 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 release ...
s 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 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 (238U ...
(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 emittin ...
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 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,"A Gentleman of Strathcona – Alexander Cameron Rutherfor ...
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 ...
, 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 Vancouver and in Kelowna, British Columbia. Established in 1908, it is British Columbia's oldest university. The university ranks a ...
,
TRIUMF TRIUMF is Canada's national particle accelerator centre. It is considered Canada's premier physics laboratory, and consistently regarded as one of the world's leading subatomic physics research centers. Owned and operated by a consortium of uni ...
,
University of Saskatchewan A university () is an institution of higher (or tertiary) education and research which awards academic degrees in several academic disciplines. Universities typically offer both undergraduate and postgraduate programs. In the United States, t ...
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, grad ...
. 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 transpo ...
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 The sievert (symbol: SvNot be confused with the sverdrup or the svedberg, two non-SI units that sometimes use the same symbol.) is a unit in the International System of Units (SI) intended to represent the stochastic health risk of ionizing radi ...
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 a beta particle (fast energetic electron or positron) is emitted from an atomic nucleus, transforming the original nuclide to an isobar of that nuclide. For ...
. Over 87% of the decays lead to the excited state of 99mTc. A
electron The electron ( or ) is a subatomic particle with a negative one elementary electric charge. Electrons belong to the first generation of the lepton particle family, and are generally thought to be elementary particles because they have no kn ...
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 ''Bremsstrahlung'' (), from "to brake" and "radiation"; i.e., "braking radiation" or "deceleration radiation", is electromagnetic radiation produced by the deceleration of a charged particle when deflected by another charged particle, typicall ...
''). 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, 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 ...
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 99mTc isotope (half-life 6 hou ...
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; as in washing of loaded ion-exchange resins to remove captured ions. In a liquid chromatography experiment, for exam ...
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 charge of an atom if all of its bonds to different atoms were fully ionic. It describes the degree of oxidation (loss of electrons) of an atom in a chemical compound. C ...
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 of the bone. It can help diagnose a number of bone conditions, including cancer of the bone or metastasis, location of bone inflammation and fractures (that may not be visi ...
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 commonly reducing agents include the Earth meta ...
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 (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 electr ...
is added to form a
coordination complex A coordination complex consists of a central atom or ion, which is usually metallic and is called the ''coordination centre'', and a surrounding array of bound molecules or ions, that are in turn known as ''ligands'' or complexing agents. Many ...
. 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 al ...
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 Technetium (99mTc) sestamibi (INN) (commonly sestamibi; USP: technetium Tc 99m sestamibi; trade name Cardiolite) is a pharmaceutical agent used in nuclear medicine imaging. The drug is a coordination complex consisting of the radioisotope techn ...
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 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 ...
. 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 is ...
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 v ...
,
myocardium Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that ...
,
thyroid The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The thy ...
,
lung The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...
s,
liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
,
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 ...
,
kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...
s,
skeleton A skeleton is the structural frame that supports the body of an animal. There are several types of skeletons, including the exoskeleton, which is the stable outer shell of an organism, the endoskeleton, which forms the support structure inside ...
,
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 in the c ...
, 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 al ...
(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 fluid ...
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 motor ...
gamma ray A gamma ray, also known as gamma radiation (symbol γ or \gamma), is a penetrating form of electromagnetic radiation arising from the radioactive decay of atomic nuclei. It consists of the shortest wavelength electromagnetic waves, typically ...
s (these are about the same wavelength as emitted by conventional X-ray diagnostic equipment), and its
half-life Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable ato ...
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 Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable ato ...
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 Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates. CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the bra ...
. 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 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 The curie (symbol Ci) is a non- SI unit of radioactivity originally defined in 1910. According to a notice in ''Nature'' at the time, it was to be named in honour of Pierre Curie, but was considered at least by some to be in honour of Marie Curi ...
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 roentgen equivalent man (rem) is a CGS unit of equivalent dose, effective dose, and committed dose, which are dose measures used to estimate potential health effects of low levels of ionizing radiation on the human body. Quantities measur ...
), the equivalent of about 500
chest X-ray A chest radiograph, called a chest X-ray (CXR), or chest film, is a projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures. Chest radiographs are the most common film taken in med ...
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 ion ...
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 molecule i ...
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 or 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 ...
. 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 tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera (that is, ...
(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 of the bone. It can help diagnose a number of bone conditions, including cancer of the bone or metastasis, location of bone inflammation and fractures (that may not be visi ...
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 A sestamibi parathyroid scan is a procedure in nuclear medicine which is performed to localize parathyroid adenoma, which causes Hyperparathyroidism. Adequate localization of parathyroid adenoma allows the surgeon to use a minimally invasive surgi ...
which is performed using the 99mTc radioligand
sestamibi Technetium (99mTc) sestamibi (INN) (commonly sestamibi; USP: technetium Tc 99m sestamibi; trade name Cardiolite) is a pharmaceutical agent used in nuclear medicine imaging. The drug is a coordination complex consisting of the radioisotope techn ...
, and can be done in either SPECT or SPECT/CT machines.


Bone scan

The
nuclear medicine Nuclear medicine or nucleology is a medical specialty involving the application of radioactive substances in the diagnosis and treatment of disease. Nuclear imaging, in a sense, is "radiology done inside out" because it records radiation emitting ...
technique commonly called the
bone scan A bone scan or bone scintigraphy is a nuclear medicine imaging technique of the bone. It can help diagnose a number of bone conditions, including cancer of the bone or metastasis, location of bone inflammation and fractures (that may not be visi ...
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) using 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 language, Greek combining forms for "bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cell (biology), cells with a single Cell nucleus, nucleus that synthesize bone. However, in the p ...
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 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 orthophosphoric acid . The phosphate or orthophosphate ion is derived from phospho ...
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), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of atherosclerotic pla ...
. The underlying principle is, under conditions of stress, diseased
myocardium Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that ...
receives less blood flow than normal myocardium. MPI is one of several types of
cardiac stress test A cardiac stress test (also referred to as a cardiac diagnostic test, cardiopulmonary exercise test, or abbreviated CPX test) is a cardiological test that measures the heart's ability to respond to external stress in a controlled clinical environ ...
. As a
nuclear stress test A cardiac stress test (also referred to as a cardiac diagnostic test, cardiopulmonary exercise test, or abbreviated CPX test) is a cardiological test that measures the heart's ability to respond to external stress in a controlled clinical environ ...
, 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 whi ...
(Myoview,
GE Healthcare GE HealthCare is a subsidiary of American multinational conglomerate General Electric incorporated in New York and headquartered in Chicago, Illinois. As of 2017, it is a manufacturer and distributor of diagnostic imaging agents and radiopharma ...
) or 99mTc-
sestamibi Technetium (99mTc) sestamibi (INN) (commonly sestamibi; USP: technetium Tc 99m sestamibi; trade name Cardiolite) is a pharmaceutical agent used in nuclear medicine imaging. The drug is a coordination complex consisting of the radioisotope techn ...
(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 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 building ...
,
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 (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 s ...
(Persantine), which increase the heart rate or by
regadenoson Regadenoson, sold under the brand name Lexiscan among others, is an A2A adenosine receptor agonist that is a coronary vasodilator that is commonly used in pharmacologic stress testing. It produces hyperemia quickly and maintains it for a duration ...
(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), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of atherosclerotic pla ...
,
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 Cardiomyopathy is a group of diseases that affect 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 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 A cardiac stress test (also referred to as a cardiac diagnostic test, cardiopulmonary exercise test, or abbreviated CPX test) is a cardiological test that measures the heart's ability to respond to external stress in a controlled clinical environ ...
, 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, called a chest X-ray (CXR), or chest film, is a projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures. Chest radiographs are the most common film taken in med ...
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 al ...
). 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 disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...
. 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, r ...
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 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 lymphocytes that includ ...
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 re ...
or
malignant melanoma Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the Biological pigment, pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, i ...
. 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 diseas ...
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. Methylene blue is a thiazine dye. As a medication, it is mainly used to treat methemoglobinemia by converting the ferric iron in hemoglobin ...
or
isosulfan blue Isosulfan blue, sold under the brand name Lymphazurin among others, is a contrast agent medication used to delineate the lymphatic vessel The lymphatic vessels (or lymph vessels or lymphatics) are thin-walled vessels (tubes), structured lik ...
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 Immunoscintigraphy is a nuclear medicine procedure used to find cancer cells in the body by injecting a radioactively labeled antibody, which binds predominantly to cancer cells and then scanning for concentrations of radioactive emissions. Cl ...
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 ca ...
, an
immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
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, respo ...
, 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
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 GI tract contains all the major organs of the digestive system, in humans ...
s. These modified antibodies are sold by the German company
Hoechst Hoechst, Hochst, or Höchst may refer to: * Hoechst AG, a former German life-sciences company * Hoechst stain, one of a family of fluorescent DNA-binding compounds * Höchst (Frankfurt am Main), a city district of Frankfurt am Main, Germany ** Fra ...
(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 Tin is a chemical element with the symbol Sn (from la, stannum) and atomic number 50. Tin is a silvery-coloured 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, t ...
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 The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
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, ventricle, gall bladder, ...
, 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 other ...
ion with 99mTc adheres to
calcium Calcium is a chemical element with the 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 ...
deposits in damaged
heart The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide t ...
muscle, making it useful to gauge damage after a
heart attack A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may tr ...
.


Sulfur colloid for spleen scan

The
sulfur Sulfur (or sulphur in British English) is a chemical element with the symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms form cyclic octatomic molecules with a chemical formula ...
colloid of 99mTc is scavenged by the
spleen The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .
, 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 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 depen ...
*
Isotopes of technetium Technetium (43Tc) is one of the two elements with that have no stable isotopes; the other such element is promethium. – Elements marked with a * have no stable isotope: 43, 61, and 83 and up. It is primarily artificial, with only trace q ...
*
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

* * *


External links


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