Technetium-99m (
99mTc) is a
metastable nuclear isomer of
technetium-99 (itself an isotope of
technetium), symbolized as
99mTc, that is used in tens of millions of medical diagnostic procedures annually, making it the most commonly used
medical radioisotope
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 and can be detected in the body by medical equipment (
gamma cameras). It is well suited to the role, because it emits readily detectable
gamma rays with a
photon energy
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 (these 8.8 pm
photons are about the same wavelength as emitted by conventional X-ray diagnostic equipment) and its
half-life for gamma emission is 6.0058 hours (meaning 93.7% of it decays to
99Tc in 24 hours). The relatively "short" physical
half-life of the isotope and its
biological half-life of 1 day (in terms of human activity and metabolism) allows for scanning procedures which collect data rapidly but keep total patient radiation exposure low. The same characteristics make the isotope unsuitable for therapeutic use.
Technetium-99m was discovered as a product of
cyclotron 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, a radionuclide with a longer half-life (2.75 days), which decays to
99mTc. This longer decay time allows for
99Mo to be shipped to medical facilities, where
99mTc is extracted from the sample as it is produced. In turn,
99Mo is usually created commercially by fission of
highly enriched uranium in a small number of research and material testing nuclear reactors in several countries.
History
Discovery
In 1938,
Emilio Segrè and
Glenn T. Seaborg isolated for the first time the
metastable isotope technetium-99m, after bombarding natural molybdenum with 8 MeV
deuterons in the
cyclotron 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. 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, Walter Tucker and
Margaret Greene were working on how to improve the separation process purity of the short-lived
eluted daughter product 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 (with a half life of 3.2 days), produced in the Brookhaven Graphite Research Reactor. They detected a trace contaminant which proved to be
99mTc, which was coming from
99Mo and was following tellurium in the chemistry of the separation process for other fission products. Based on the similarities between the chemistry of the tellurium-iodine parent-daughter pair, Tucker and Greene developed the first
technetium-99m generator in 1958. It was not until 1960 that Richards became the first to suggest the idea of using technetium as a medical tracer.
The first US publication to report on medical scanning of
99mTc appeared in August 1963.
Sorensen and Archambault demonstrated that intravenously injected carrier-free
99Mo selectively and efficiently concentrated in the liver, becoming an internal generator of
99mTc. After build-up of
99mTc, they could visualize the liver using the 140 keV gamma ray emission.
Worldwide expansion
The production and medical use of
99mTc rapidly expanded across the world in the 1960s, benefiting from the development and continuous improvements of the
gamma cameras.
Americas
Between 1963 and 1966, numerous scientific studies demonstrated the use of
99mTc as
radiotracer or diagnostic tool. As a consequence the demand for
99mTc grew exponentially and by 1966,
Brookhaven National Laboratory was unable to cope with the demand. Production and distribution of
99mTc generators were transferred to private companies. ''"TechneKow-CS generator"'', the first commercial
99mTc generator, was produced by Nuclear Consultants, Inc. (St. Louis, Missouri) and
Union Carbide Nuclear Corporation (Tuxedo, New York). From 1967 to 1984,
99Mo was produced for
Mallinckrodt Nuclear Company at the
Missouri University Research Reactor (MURR).
Union Carbide actively developed a process to produce and separate useful isotopes like
99Mo from mixed
fission products
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 (HEU) targets in nuclear reactors developed from 1968 to 1972 at the Cintichem facility (formerly the Union Carbide Research Center built in the Sterling forest in Tuxedo, New York ()). The Cintichem process originally used 93% highly enriched U-235 deposited as UO
2 on the inside of a cylindrical target.
At the end of the 1970s, of total fission product radiation were extracted weekly from 20-30 reactor bombarded HEU capsules, using the so-called "Cintichem
hemical isolationprocess." The research facility with its 1961 5-MW pool-type research reactor was later sold to Hoffman-LaRoche and became Cintichem Inc. In 1980, Cintichem, Inc. began the production/isolation of
99Mo in its reactor, and became the single U.S. producer of
99Mo during the 1980s. However, in 1989, Cintichem detected an underground leak of radioactive products that led to the reactor shutdown and decommissioning, putting an end to the commercial production of
99Mo in the USA.
The production of
99Mo started in Canada in the early 1970s and was shifted to the NRU reactor in the mid 1970s. By 1978 the reactor provided technetium-99m in large enough quantities that were processed by AECL's radiochemical division, which was privatized in 1988 as Nordion, now
MDS Nordion. In the 1990s a substitution for the aging NRU reactor for production of radioisotopes was planned. The
Multipurpose Applied Physics Lattice Experiment
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, each capable of supplying 100% of the world's medical isotope demand. However, problems with the MAPLE 1 reactor, most notably a positive
power co-efficient of reactivity, led to the cancellation of the project in 2008.
The first commercial
99mTc generators were produced in
Argentina in 1967, with
99Mo produced in the
CNEA's
RA-1 Enrico Fermi 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,
New Zealand.
99Mo was initially supplied by Amersham, UK, then by the Australian Nuclear Science and Technology Organisation (
ANSTO) in Lucas Heights, Australia.
Europe
In May 1963, Scheer and Maier-Borst were the first to introduce the use of
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 announced the detection of a small leak of
heavy water in the NRU reactor that remained out of service until completion of the repairs in August 2010. After the observation of gas bubble jets released from one of the deformations of primary cooling water circuits in August 2008, the HFR reactor was stopped for a thorough safety investigation.
NRG received in February 2009 a temporary license to operate HFR only when necessary for medical radioisotope production. HFR stopped for repairs at the beginning of 2010 and was restarted in September 2010.
Two replacement Canadian reactors (see
MAPLE Reactor) constructed in the 1990s were closed before beginning operation, for safety reasons.
A construction permit for a new production facility to be built in
Columbia, MO was issued in May 2018.
Nuclear properties
Technetium-99m is a metastable
nuclear isomer, as indicated by the "m" after its
mass number 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 rays or
internal conversion electrons. Both of these decay modes rearrange the
nucleons without
transmuting the technetium into another element.
99mTc decays mainly by gamma emission, slightly less than 88% of the time. (
99mTc →
99Tc + γ) About 98.6% of these gamma decays result in 140.5 keV gamma rays and the remaining 1.4% are to gammas of a slightly higher energy at 142.6 keV. These are the radiations that are picked up by a gamma camera when
99mTc is used as a
radioactive tracer for
medical imaging
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, resulting in ejection of high speed internal conversion electrons in several sharp peaks (as is typical of electrons from this type of decay) also at about 140 keV (
99mTc →
99Tc
+ + e
−). These conversion electrons will
ionize the surrounding matter like
beta radiation electrons would do, contributing along with the 140.5 keV and 142.6 keV gammas to the total deposited
dose
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 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
radiopharmaceuticals 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 reactors around the world using
highly enriched uranium (HEU) targets. Smaller amounts of
99Mo are produced from
low-enriched uranium in at least three reactors.
Neutron activation of 98Mo
Production of
99Mo by
neutron activation of natural molybdenum, or molybdenum enriched in
98Mo, is another, currently smaller, route of production.
Production of 99mTc/99Mo in particle accelerators
Production of "Instant" 99mTc
The feasibility of
99mTc production with the 22-MeV-proton bombardment of a
100Mo target in medical cyclotrons was demonstrated in 1971. The recent shortages of
99mTc reignited the interest in the production of "instant" 99mTc by proton bombardment of isotopically enriched
100Mo targets (>99.5%) following the reaction
100Mo(p,2n)
99mTc. Canada is commissioning such cyclotrons, designed by
Advanced Cyclotron Systems
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 ...
, for
99mTc production at the
University of Alberta and the
Université de Sherbrooke, and is planning others at the
University of British Columbia,
TRIUMF,
University of Saskatchewan and
Lakehead University.
A particular drawback of cyclotron production via (p,2n) on
100Mo is the significant co-production of
99gTc. The preferential in-growth of this nuclide occurs due to the larger reaction cross-section pathway leading to the ground state, which is almost five times higher at the cross-section maximum in comparison with the metastable one at the same energy. Depending on the time required to process the target material and recovery of
99mTc, the amount of
99mTc relative to
99gTc will continue to decrease, in turn reducing the specific activity of
99mTc available. It has been reported that ingrowth of
99gTc as well as the presence of other Tc isotopes can negatively affect subsequent labelling and/or imaging; however, the use of high purity
100Mo targets, specified proton beam energies, and appropriate time of use have shown to be sufficient for yielding
99mTc from a cyclotron comparable to that from a commercial generator. Liquid metal molybdenum-containing targets have been proposed that would aid in streamlined processing, ensuring better production yields. A particular problem associated with the continued reuse of recycled, enriched
100Mo targets is unavoidable transmutation of the target as other Mo isotopes are generated during irradiation and cannot be easily removed post-processing.
Indirect routes of production of 99Mo
Other particle accelerator-based isotope production techniques have been investigated. The supply disruptions of
99Mo in the late 2000s and the ageing of the producing nuclear reactors forced the industry to look into alternative methods of production. The use of cyclotrons or electron accelerators to produce
99Mo from
100Mo via (p,pn) or (γ,n) reactions, respectively, has been further investigated. The (n,2n) reaction on
100Mo yields a higher reaction cross-section for high energy neutrons than of (n,γ) on
98Mo with thermal neutrons. In particular, this method requires accelerators that generate fast neutron spectrums, such as ones using D-T or other fusion-based reactions, or high energy spallation or knock out reactions. A disadvantage of these techniques is the necessity for enriched
100Mo targets, which are significantly more expensive than natural isotopic targets and typically require recycling of the material, which can be costly, time consuming, and arduous.
Technetium-99m generators
Technetium-99m's short half-life of 6 hours makes storage impossible and would make transport very expensive. Instead, its parent nuclide
99Mo is supplied to hospitals after its extraction from the neutron-irradiated uranium targets and its purification in dedicated processing facilities.
It is shipped by specialised radiopharmaceutical companies in the form of
technetium-99m generators worldwide or directly distributed to the local market. The generators, colloquially known as moly cows, are devices designed to provide radiation shielding for transport and to minimize the extraction work done at the medical facility. A typical dose rate at 1 metre from the
99mTc generator is 20-50
μSv/h during transport. These generators' output declines with time and must be replaced weekly, since the half-life of
99Mo is still only 66 hours.
Molybdenum-99 spontaneously decays to excited states of
99Tc through
beta decay. Over 87% of the decays lead to the excited state of
99mTc. A
electron and a
electron antineutrino are emitted in the process (
99Mo →
99mTc + + ). The electrons are easily
shielded for transport, and
99mTc generators are only minor radiation hazards, mostly due to secondary X-rays produced by the electrons (also known as ''
Bremsstrahlung'').
At the hospital, the
99mTc that forms through
99Mo decay is chemically extracted from the technetium-99m generator. Most commercial
99Mo/
99mTc generators use
column chromatography, in which
99Mo in the form of water-soluble molybdate, MoO
42− is
adsorbed onto acid alumina (Al
2O
3). When the
99Mo decays, it forms
pertechnetate TcO
4−, which, because of its single charge, is less tightly bound to the alumina. Pulling normal saline solution through the column of immobilized
99MoO
42− 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
99mTcO
4−, resulting in a saline solution containing the
99mTc as the dissolved
sodium salt of the pertechnetate. One technetium-99m generator, holding only a few micrograms of
99Mo, can potentially diagnose 10,000 patients because it will be producing
99mTc strongly for over a week.
Preparation
Technetium exits the generator in the form of the pertechnetate ion, TcO
4−. The
oxidation state of Tc in this compound is +7. This is directly suitable for medical applications only in
bone scans (it is taken up by osteoblasts) and some thyroid scans (it is taken up in place of iodine by normal thyroid tissues). In other types of scans relying on
99mTc, a
reducing agent is added to the pertechnetate solution to bring the oxidation state of the technecium down to +3 or +4. Secondly, a
ligand is added to form a
coordination complex. The ligand is chosen to have an affinity for the specific organ to be targeted. For example, the
exametazime
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 to measure renal function.
[ Historical perspective, full text]
Medical uses
In 1970, Eckelman and Richards presented the first "kit" containing all the ingredients required to release the
99mTc, "milked" from the generator, in the chemical form to be administered to the patient.
Technetium-99m is used in 20 million diagnostic nuclear medical procedures every year. Approximately 85% of diagnostic imaging procedures in nuclear medicine use this isotope as radioactive tracer. Klaus Schwochau's book ''Technetium'' lists 31 radiopharmaceuticals based on 99mTc for imaging and functional studies of the brain, 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, 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, gallbladder, kidneys, 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, and tumors. 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
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 ...
); 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 gamma rays (these are about the same wavelength as emitted by conventional X-ray diagnostic equipment), and its half-life for gamma emission is six hours (meaning 94% of it decays to 99Tc in 24 hours). Besides, it emits no particle radiation, thus keeping radiation dosage low. Its decay product, 99Tc, has a relatively long half-life (211,000 years) and emits little radiation. The short physical half-life of 99mTc and its biological half-life of 1 day with its other favourable properties allows scanning procedures to collect data rapidly and keep total patient radiation exposure low. Chemically, technetium is selectively concentrated in thyroid, salivary glands, and stomach and excluded from cerebrospinal fluid. Combination with perchlorate abolishes its selectiveness.
Radiation side-effects
Diagnostic treatment involving technetium-99m will result in radiation exposure to technicians, patients, and passers-by. Typical quantities of technetium administered for immunoscintigraphy tests, such as SPECT tests, range from (millicurie
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 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 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 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 which computes and processes the image. To acquire SPECT images, the gamma camera is rotated around the patient. Projections are acquired at defined points during the rotation, typically every three to six degrees. In most cases, a full 360° rotation is used to obtain an optimal reconstruction. The time taken to obtain each projection is also variable, but 15–20 seconds are typical. This gives a total scan time of 15–20 minutes.
The technetium-99m radioisotope is used predominantly in bone and brain scans. For bone scans, the pertechnetate ion is used directly, as it is taken up by osteoblasts attempting to heal a skeletal injury, or (in some cases) as a reaction of these cells to a tumor (either primary or metastatic) in the bone. In brain scanning, 99mTc is attached to the chelating agent HMPAO to create technetium (99mTc) exametazime, an agent which localizes in the brain according to region blood flow, making it useful for the detection of stroke and dementing illnesses that decrease regional brain flow and metabolism.
Most recently, technetium-99m scintigraphy has been combined with CT coregistration technology to produce SPECT/CT scans. These employ the same radioligands and have the same uses as SPECT scanning, but are able to provide even finer 3-D localization of high-uptake tissues, in cases where finer resolution is needed. An example is the sestamibi parathyroid scan
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 technique commonly called the bone scan usually uses 99mTc. It is not to be confused with the "bone density scan", DEXA, which is a low-exposure X-ray test measuring bone density to look for osteoporosis and other diseases where bones lose mass without rebuilding activity. The nuclear medicine technique is sensitive to areas of unusual bone rebuilding activity, since the radiopharmaceutical is taken up by osteoblast
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. Medronic acid is a phosphate derivative which can exchange places with bone phosphate in regions of active bone growth, so anchoring the radioisotope to that specific region. To view small lesions (less than ) especially in the spine, the SPECT imaging technique may be required, but currently in the United States, most insurance companies require separate authorization for SPECT imaging.
Myocardial perfusion imaging
Myocardial perfusion imaging (MPI) is a form of functional cardiac imaging, used for the diagnosis of ischemic heart disease
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) 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) 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 or dipyridamole(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, 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, congenital heart diseases, 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 disorders. 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. When used with the 3-D SPECT technique, they compete with brain FDG-PET scans and fMRI brain scans as techniques to map the regional metabolic rate of brain tissue.
Sentinel-node identification
The radioactive properties of 99mTc can be used to identify the predominant lymph nodes draining a cancer, such as breast cancer or malignant melanoma. This is usually performed at the time of biopsy or resection.99mTc-labelled filtered sulfur colloid or Technetium (99mTc) tilmanocept
Technetium (99mTc) tilmanocept, trade name Lymphoseek, is a radiopharmaceutical diagnostic imaging agent used to locate lymph nodes which may be draining from tumors, and assist doctors in locating lymph nodes for removal during surgery.
The m ...
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, an immune system protein, capable of binding to cancer cells. A few hours after injection, medical equipment is used to detect the gamma rays emitted by the 99mTc; higher concentrations indicate where the tumor is. This technique is particularly useful for detecting hard-to-find cancers, such as those affecting the 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) under the name "Scintium".
Blood pool labeling
When 99mTc is combined with a tin compound, it binds to red blood cells and can therefore be used to map circulatory system disorders. It is commonly used to detect gastrointestinal bleeding sites as well as ejection fraction, heart wall motion abnormalities, abnormal shunting, and to perform ventriculography.
Pyrophosphate for heart damage
A pyrophosphate ion with 99mTc adheres to calcium deposits in damaged heart muscle, making it useful to gauge damage after a heart attack.
Sulfur colloid for spleen scan
The sulfur
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, making it possible to image the structure of the spleen.
Meckel's diverticulum
Pertechnetate is actively accumulated and secreted by the mucoid cells of the gastric mucosa, and therefore, technetate(VII) radiolabeled with Tc99m is injected into the body when looking for ectopic gastric tissue as is found in a Meckel's diverticulum with Meckel's Scans.
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
* Transient equilibrium
Notes
References
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Further reading
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External links
99mTc production simulator – IAEA
{{DEFAULTSORT:Technetium-099m
Metastable isotopes
Medical physics
Radiopharmaceuticals
Radiochemistry
Medicinal radiochemistry