Technetium-99m is a metastable nuclear isomer of technetium-99, symbolized as 99mTc. The "m" indicates that this is a metastable nuclear isomer, i.e., that its half-life of 6 hours is considerably longer (by 14 orders of magnitude, at least) than most nuclear isomers that undergo gamma decay. The life-time of technetium-99m is very long in terms of average gamma-decay half-lives, though short in comparison with half-lives for other kinds of radioactive decay, and in comparison with radionuclides used in many kinds of nuclear medicine tests.
Technetium-99m is used as a radioactive tracer that medical equipment can detect in the body. It is well suited to the role because it emits readily detectable 140 keV gamma rays (these are about the same wavelength emitted by conventional X-ray diagnostic equipment), and its half-life for gamma emission is 6.0058 hours (meaning that 93.7% of it decays to 99Tc in 24 hours). The "short" half-life of the isotope (in terms of human-activity and metabolism) allows for scanning procedures which collect data rapidly, but keep total patient radiation exposure low.
As in all gamma decay reactions, a metastable nuclear isomer does not change into another element (transmute) upon its isomeric transition or "decay"; thus 99mTc decays to technetium-99 (Tc-99, the ground state of the same isotope) and remains technetium. The decay of technetium-99m is accomplished by rearrangement of nucleons in its nucleus, a process that allows energy to be emitted as a gamma ray.
The resulting technetium-99 then decays to stable ruthenium-99 with a half-life of 211,000 years. It emits soft beta particles (electrons) in this process, but no gamma rays (photons). All of these characteristics ensure that the technetium-99 produced from technetium-99m produces very little extra radiation burden on the body.
Due to its short half-life, technetium-99m for nuclear medicine purposes is usually extracted from technetium-99m generators which contain molybdenum-99 (Mo-99, half-life 2.75 days), which is the usual parent nuclide for this isotope. The majority of Mo-99 produced for Tc-99m medical use comes from fission of HEU (highly enriched uranium) from only five reactors around the world: NRU, Canada; BR2, Belgium; SAFARI-1, South Africa; HFR (Petten), the Netherlands; and the OSIRIS reactor in Saclay, France.[1][2] Production from LEU (low-enriched uranium) is possible, and is produced at the new OPAL reactor, Australia, as well as other sites. Activation of Mo-98 is another, currently smaller, route of production.[3]
Demand for medical use of Mo-99 to make Tc-99m began to overtake a dwindling supply, in the late 2000s.
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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.[4][5] Two replacement Canadian reactors constructed in the 1990s were closed before beginning operation, for safety reasons.[4]
Technetium-99m or 99mTc ("m" indicates that this is a metastable nuclear isomer) is used in radioactive isotope medical tests: for example, as a radioactive tracer that medical equipment can detect in the human body.[6] It is well-suited to the role because it emits readily detectable 140 keV gamma rays, and its half-life is only about six hours. It dissolves in aqua regia, nitric acid, and concentrated sulfuric acid, but it is not soluble in hydrochloric acid of any strength.[7] Klaus Schwochau's book Technetium lists 31 radiopharmaceuticals based on 99mTc for imaging and functional studies of the brain, myocardium, thyroid, lungs, liver, gallbladder, kidneys, skeleton, blood, and tumors.[8]
Technetium-99m is used in 20 million diagnostic nuclear medical procedures every year. Approximately 85 percent of diagnostic imaging procedures in nuclear medicine use this isotope. Depending on the type of nuclear medicine procedure, the 99mTc is tagged (or bound to) a pharmaceutical that transports the Tc-99m to its required location. For example, when 99mTc is chemically bound to exametazime, 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 to visualize sites of infection. 99mTc Sestamibi is used for myocardial perfusion imaging, which shows how well the blood flows through the heart. Imaging to measure renal function is done by attaching 99mTc to Mercapto acetyl triglycine (informal acronym: MAG3); this procedure is known as a MAG3 scan.
Molybdenum-99 has a half-life of approximately 66 hours (2.75 days), and decays to 99mTc through beta decay, emitting an electron and an antineutrino in the process (see equation below). This is a useful life since once molybdenum-99 is created, it can be transported to any hospital in the world and still is able to produce its decay product technetium-99m over the next week. The electrons produced from the decay of Mo-99 are easily absorbed, and Mo-99 generators are only minor radiation hazards, mostly due to secondary X-rays produced by the electrons (also known as bremsstrahlung).
The decay process that produces 99mTc:
can also be written as
where e−
(or β−
) denotes the electron (beta particle) emitted from the nucleus, and ν
e denotes the emitted antineutrino (or more specifically, an electron antineutrino).
Most commercial 99Mo/99mTc generators use column chromatography, in which 99Mo in the form of molybdate, MoO42- is adsorbed onto acid alumina (Al2O3). When the 99Mo decays it forms pertechnetate TcO4-, which because of its single charge is less tightly bound to the alumina. Pulling normal saline solution through the column of immobilized 99Mo elutes the soluble 99mTc, resulting in a saline solution containing the 99mTc as the dissolved sodium salt of the pertechnetate.
99mTc will then undergo an isomeric transition to yield 99Tc and a monoenergetic gamma emission:
This is the process that happens inside the patient, and which is picked up by the gamma camera.
When a hospital receives a technetium-99m generator containing molybdenum-99, the technetium-99m that forms through 99Mo decay can be chemically extracted easily. One technetium-99m generator, holding only a few micrograms of 99Mo, can potentially diagnose ten thousand patients because it will be producing 99mTc strongly for over a week. 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.
Typical quantities of technetium administered for immunoscintigraphy tests, such as SPECT tests, range from 10 to 30 mCi for adults.[9][10] These doses result in radiation exposures to the patient around 10 mSv, the equivalent of about 500 chest X-ray exposures.[11]
Radiation exposure due to diagnostic treatment involving technetium-99m can be kept low. Because technetium-99m has a short half-life and emits primarily a gamma ray (allowing small amounts to be easily detected), its quick decay into the far-less radioactive technetium-99 results in relatively low total radiation dose to the patient per unit of initial activity after administration, as compared to other radioisotopes. In the form administered in these medical tests (usually pertechnetate), technetium-99m and technetium-99 are eliminated from the body within a few days.[12] Technetium for nuclear medicine purposes is extracted from technetium-99m generators, because of its short 6-hour half-life.[13]
Radiation exposure with technetium-99m is associated with a potential, small, risk of inducing cancer in the patient later in life and is higher in younger patients.[14]
Single photon emission computed tomography (SPECT) is a nuclear medicine imaging technique using gamma rays. It may be used with any gamma-emitting isotope, including Tc-99m. In the use of technetium-99m, the radioisotope is administered to the patient and the escaping gamma rays are incident upon a moving gamma camera which computes and processes the image. To acquire SPECT images, the gamma camera is rotated around the patient. Projections are acquired at defined points during the rotation, typically every 3-6 degrees. In most cases, a full 360 degree rotation is used to obtain an optimal reconstruction. The time taken to obtain each projection is also variable, but 15–20 seconds is typical. This gives a total scan time of 15–20 minutes. The technetium-99m radioisotope is used predominantly in both bone and brain scans to check for any irregularities. Although Tc-99m is used for diagnostic nuclear medicine imaging procedures, it is not used for any therapeutic procedures.
Technetium comes off the generator in the form of the pertechnetate ion, TcO4-. The oxidation state of Tc in this compound is +7. This is not suitable for medical applications. In medical practice, a reducing agent is added to the pertechnetate solution to bring the oxidation state down to +3 or +4. Secondly a ligand is added to form a coordination complex. The ligand is chosen to have an affinity for the specific organ to be targeted. For example, the exametazime complex of Tc in oxidation state +3 is able to cross the blood-brain barrier and flow through the vessels in the brain for cerebral blood flow imaging. Other ligands include Sestamibi for myocardial perfusion imaging and Mercapto Acetyl TRIGlycine for MAG3 scan to measure renal function.[15]
The nuclear medicine technique commonly called the bone scan usually uses Tc-99m. It is not to be confused with the different "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 re-building activity. The nuclear medicine technique is sensitive to areas of unusual bone re-building activity, since the radiopharmaceutical is taken up by osteoblast cells which build bone. The technique therefore is sensitive to fractures and bone reaction to bone tumors, including metastases. For a bone scan, the patient is injected with a small amount of radioactive material such as 20-30 mCi of technetium-99m-MDP and then scanned with a gamma camera. MDP is a phosphate derivative which can exchange place with bone phosphate in regions of active bone growth, so anchoring the radioisotope to that specific region. In order to view small lesions (less than 1 cm) 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 (MPI) is a form of functional cardiac imaging, used for the diagnosis of ischemic heart disease. The underlying principle is that under conditions of stress, diseased myocardium receives less blood flow than normal myocardium. MPI is one of several types of cardiac stress test.
Several radiopharmaceuticals and radionuclides may be used for this, each giving different information. In the myocardial perfusion scans using Tc-99m, the radiopharmaceuticals 99mTc-tetrofosmin (Myoview, GE Healthcare) or 99mTc-sestamibi (Cardiolite, Bristol-Myers Squibb) are used. Following this, the heart rate is raised to induce myocardial stress, either by exercise or pharmacologically with adenosine, dobutamine or dipyridamole (aminophylline can be used to reverse the effects of dipyridamole). Scanning may then be performed with a conventional gamma camera, or with SPECT.
In cardiac ventriculography, a radionuclide, which usually is 99mTc, is injected, and the heart is imaged to evaluate the flow through it. This test is done to evaluate coronary artery disease (CAD), valvular heart disease, congenital heart diseases, cardiomyopathy, and other cardiac disorders.[16] It exposes patients to less radiation than do comparable chest x-ray studies.[16]
Usually the gamma-emitting tracer used in functional brain imaging is 99mTc-HMPAO (hexamethylpropylene amine oxime, exametazime). The similar 99mTc-EC tracer may also be used. These molecules are preferentially distributed to regions of high brain blood flow, and act to assess brain metabolism regionally, in an attempt to diagnose and differentiate the different causal pathologies of dementia. When used with the 3-D SPECT technique, they compete with brain FDG-PET scans and fMRI brain scans as techniques to map the regional metabolic rate of brain tissue.
The radioactive properties of 99mTc can be used to identify the predominant lymph nodes draining a cancer, such as breast cancer or malignant melanoma. This is usually performed at the time of biopsy or resection. 99mTc-labelled isosulfan blue dye is injected intradermally around the intended biopsy site. The general location of the sentinel node is determined with the use of a handheld scanner with a gamma-sensor probe that detects the technetium-99m–labeled sulfur colloid that was previously injected around the biopsy site. An incision is then made over the area of highest radionuclide accumulation, and the sentinel node is identified within the incision by inspection; the isosulfan blue dye will usually stain any draining nodes blue.[17]
Immunoscintigraphy incorporates 99mTc into a monoclonal antibody, an immune system protein, capable of binding to cancer cells. A few hours after injection, medical equipment is used to detect the gamma rays emitted by the 99mTc; higher concentrations indicate where the tumor is. This technique is particularly useful for detecting hard-to-find cancers, such as those affecting the intestine. These modified antibodies are sold by the German company Hoechst (now part of Sanofi-Aventis) under the name "Scintium".[6]
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.
A pyrophosphate ion with 99mTc adheres to calcium deposits in damaged heart muscle, making it useful to gauge damage after a heart attack.[12]
The sulfur colloid of 99mTc is scavenged by the spleen, making it possible to image the structure of the spleen.[7]
| Lighter: technetium-99 |
Technetium-99m is an isotope of technetium |
Heavier: Technetium-100 |
| Decay product of: molybdenum-99 |
Decay chain of Technetium-99m |
Decays to: Technetium-99 |
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