Technetium-99m is a metastable nuclear isomer of technetium-99 (itself a technetium isotope), denoted as 99m Tc, used in tens of millions of medical diagnostic procedures each year, making it radioisotopes the most commonly used medical.
Technetium-99m is used as a radioactive tracer and can be detected in the body by medical equipment (gamma camera). It is suitable for this role, because it emits gamma rays that are readily detected with photon energy of 140 keV (8.8 μm photons have the same wavelength as those emitted by conventional X-ray diagnostic equipment) and the half-life for gamma emissions is 6,0058 h ( means that 93.7% of it decays to 99 Tc in 24 hours). The relatively short half-life of the isotope isotope and the biological half-life of 1 day (in terms of human activity and metabolism) makes it possible to perform a rapid scanning procedure that collects data but keeps the patient's total radiation exposure low. The same characteristics make isotopes suitable only for diagnostic use but never therapeutic.
Technetium-99m is found as a molybdenum cyclotron firing product. This procedure produces molybdenum-99, radionuclides with a longer half-life (2.75 days), which decays into Tc-99m. Currently, molybdenum-99 (Mo-99) is used commercially as an easily transferable medical Tc-99m source. In turn, this Mo-99 is usually commercially manufactured by highly enriched uranium fission in the research of aging and testing of nuclear reactor materials in several countries.
Video Technetium-99m
Histori
Discovery
In 1938 Emilio Segra and Glenn T. Seaborg isolated for the first time metastable isotope technetium-99m, after bombarding natural molybdenum with 8 deuteron MeV in 37-inch (940Ã, mm) laboratory cyclotron Ernest Radiation Orlando Lawrence. In 1970 Seaborg explained that:
we discovered an isotope that was of great scientific interest, because it decayed through an isomeric transition with electron line spectrum emissions stemming from completely converted gamma-ray transitions internally. [actually, only 12% of decay is by internal conversion] (...) This is a form of radioactive decay that has never been observed before this time. SegrÃÆ'¨ and I can show that the radioactive isotope of this element with atomic number 43 is decomposed with a half-life of 6.6 hours [later updated to 6.0 hours] and that it is a daughter of 67-hours [later updated to 66 h ] radioactivity of molybdenum parents. This decay chain is then shown to have a mass number of 99, and (...) a 6.6 hour activity obtains a technetium-99m tagging.
Then in 1940, Emilio SegrÃÆ'¨ and Chien-Shiung Wu published the results of a fission product analysis experiment of uranium-235, among which was the presence of molybdenum-99, and detected a 6-hour elemental activity of 43, then labeled as technetium -99 m.
Initial medical applications in the US
Tc-99m remained a scientific curiosity until 1950 when Powell Richards realized the technetium-99m potential as a medical radiotracer and promoted its use among the medical community. While Richards is responsible for the production of radioisotopes in the Hot Lab Division of the Brookhaven National Laboratory, Walter Tucker and Margaret Greene are working on how to improve the purity of the separation process from the iodine-132 short birth-daughter product of the egg-132, its 3.2-day parent, produced at the Research Reactor Graphite Brookhaven. They detected traces of proven contaminants of Tc-99m, originating from Mo-99 and following tellurium in chemical separation processes for other fission products. Based on similarities between tellurium-yogium parent-daughter chemistry, Tucker and Greene developed the first technetium-99m generator in 1958 (see this generator photo at the beginning of the article). New in 1960 Richards became the first person to propose the idea of ​​using technetium as a medical tracer.
The first US publication to report the Tc-99m medical scan appeared in August 1963. Sorensen and Archambault demonstrated that intravenous oxygen-free Mo-99 was selectively and efficiently concentrated in the liver, becoming an internal Tc-99m generator. After the buildup of Tc-99m, they can visualize the liver using the 140 keV gamma-ray emission.
Worldwide expansion
The medical production and usage of Tc-99m rapidly expanded worldwide in the 1960s, benefiting from the continued development and improvement of gamma cameras.
- American Continent
Between 1963 and 1966, many scientific studies demonstrated the use of Tc-99m as a radiotracer or diagnostic tool. As a result demand for Tc-99m grew exponentially and in 1966, Brookhaven National Laboratory was unable to cope with the request. Production and distribution of Tc-99m generators were transferred to private companies. "TechneKow-CS Generator" , the first commercial Tc-99m generator, manufactured by Nuclear Consultants, Inc. (St. Louis, Missouri) and Union Carbide Nuclear Corporation (Tuxedo, New York). From 1967 to 1984, Mo-99 was produced for the Mallinckrodt Nuclear Company at the University of Missouri Research Reactor (MURR).
Union Carbide is actively developing processes for producing and separable useful isotopes such as Mo-99 from a fission mixture product resulting from highly enriched uranium irradiation (HEU) targets at nuclear reactors developed from 1968-1972 at the Cintichem facility (formerly the Union Carbide Research Center constructed in the Sterling forest in Tuxedo, New York ( 41A Â ° 14? 6.88? N 74 Â ° 12? 50,78? W )). The Cintichem process originally used 93% highly enriched U-235 is stored as UO 2 inside the cylinder target.
In the late 1970s, 200,000 Ci (7,4 ÃÆ' - 10 15 BQ) of total product fission radiation was extracted every week from 20-30 reactors bombarding HEU capsules, using the so-called "Cintichem [chemical isolation] process." The research facility with a 1961 5-MW type pool research reactor was then sold to Hoffman-LaRoche and became Cintichem Inc. In 1980, Cintichem, Inc. started production/isolation of Mo-99 in its reactor, and became a US Producer Mo-99 during the 1980s. However, in 1989, Cintichem detected a leak of underground radioactive products that led to reactor shutdown and decommissioning, ending commercial production of Mo-99 in the US.
Production of Mo-99 began in Canada in the early 1970s and was transferred to the NRU reactor in the mid-1970s. In 1978 the reactor provided a sizable technetium-99m processed by the AECL radiochemical division, which was privatized in 1988 as Nordion, now MDS Nordion. In the 1990s, a substitution for an old NRU reactor for radioisotope production was planned. Versatile Multipurpose Physical Grid Trial (MAPLE) is designed as a special isotope production facility. Initially, two identical MAPLE reactors were built in Chalk River Laboratories, each capable of supplying 100% of the world's medical isotope demand. However, problems with the MAPLE 1 reactor, particularly the positive strength of co-efficient reactivity, led to the cancellation of the project in 2008.
The first commercial Tc-99m generator was manufactured in Argentina in 1967, with Mo-99 manufactured at the ENA RA-1 Enrico Fermi CNEA. In addition to its domestic market, the CNEA supplies Mo-99 to several South American countries.
- Asia
In 1967, the first Tc-99m procedure was performed in Auckland, New Zealand. Mo-99 was originally supplied by Amersham, England, then by the Australian Institute of Nuclear Science and Technology (ANSTO) in Lucas Heights, Australia.
- Europe
In May 1963, Scheer and Maier-Borst were the first to introduce the use of Tc-99m for medical applications. In 1968, Philips-Duphar (later Mallinckrodt, today Covidien) marketed the first technetium-99m generator produced in Europe and distributed from Petten, The Netherlands.
Disadvantages
The global technetium-99m shortage emerged in the late 2000s because of two old nuclear reactors (NRU and HFR) that provided about two-thirds of the world's molybdenum-99 supply, which itself had a half-life of only 66 hours, was closed down repeatedly for periods extended maintenance. In May 2009, Atomic Energy of Canada Limited announced the detection of minor leakage of heavy water in the NRU reactor which remained non-functional until completion of the repair in August 2010. After observations of gas bubbles released from one of the deformations of the primary cooling water circuit in August 2008, the HFR reactor discontinued for thorough safety investigation. The NRG received in February 2009 a temporary license to operate HFR only when necessary for the production of medical radioisotopes. HFR ceased for repairs in early 2010 and resumed in September 2010.
Two Canadian substitute reactors (see MAPLE Reactor) built in the 1990s were shut down before starting operations, for safety reasons.
Maps Technetium-99m
Nuclear properties
Technetium-99m is a metastable nuclear isomer, as shown by "m" after its mass number 99. This means it is a decay product whose nuclei remain in an excited state that lasts longer than normal. The nucleus will eventually relax (that is, de-excite) to the ground state through gamma ray emission or internal conversion electrons. Both of these decay modes reset the nucleons without converting technetium into other elements.
Tc-99m decays primarily by gamma emissions, slightly less than 88% of the time. 99c Tc -> 99 Tc?) About 98.6% of this gamma decay produces a gamma ray of 140.5 keV and the remaining 1.4% is gammas with energy slightly higher at 142.6 keV. This is the radiation taken by the gamma camera when 99m Tc is used as a radioactive tracer for medical imaging. The remaining 12% of the decay of 99m Tc is by means of internal conversion, which results in high-speed internal electron transfer ejection at some sharp peaks (such as the typical electron of this decay type) also at about 140 keV > 99m Tc -> 99 Tc e - ). This conversion electron will ionize the surrounding material such as the beta electrons will perform, contributing together with 140.5 keV and 142.6 keV gammas with total doses deposited.
Pure gamma emission is the preferred decay mode for medical imaging because other particles store more energy in the patient's body (radiation dose) than in the camera. The metastable isomeric transition is the only nuclear decay mode that is close to pure gamma emission.
Tc-99m part-time 6,0058 hours is much longer (by 14 orders, at least) than most nuclear isomers, though not unique. This is still a short half-life relative to many other known radioactive decay modes and is in the middle of the half-life range for radiopharmaceuticals used for medical imaging.
The parent nuclides of Tc-99m, Mo-99, are primarily extracted for medical purposes from fission products made in neutron irradiated U-235 targets, most of which are manufactured in five nuclear research reactors worldwide using highly enriched uranium. (HEU) target. Smaller amounts of 99 Mo are produced from low enriched uranium in at least three reactors.
- Activation of Neutron Mo-98
Production of 99 Mo by the activation of neutrons from natural molybdenum, or molybdenum enriched in Mo-98, is yet another, smaller current, with production.
Production of Tc-99m/Mo-99 in particle accelerator
- Production of "Instant" Tc-99m
The feasibility of producing Tc-99m with 22-MeV-proton bombardment target of Mo-100 in medical cyclotron was demonstrated in 1971. The recent deficiency of Tc-99m revived interest in the production of instant "99mTc" by proton bombing. target isotope-enriched Mo-100 (& gt; 99.5%) after reaction 100 Mo (p, 2n) 99m Tc. Canada commissioned such a cyclotron, designed by Advanced Cyclotron Systems, for the production of Tc-99m at the University of Alberta and Università © de Sherbrooke, and is planning another at the University of British Columbia, TRIUMF, the University of Saskatchewan and Lakehead University.
- Indirect Mo-99 production line
Other particle accelerator-based isotope production techniques have been investigated. M-99 supply interruptions in the late 2000s and aging nuclear reactors that produced forced the industry to seek alternative methods of production. The use of cyclotron to produce Mo-99 from Mo-100 via (n, 2n) or (?, N) reactions has been investigated further.
Technetium-99m Generator
Technetium-99m's short half-life of 6 hours makes storage impossible and will make transportation very expensive. This is not the parent nucid 99 Mo supplied to the hospital after the extraction of the neutron irradiated uranium target and its purification at a special processing facility. These are sent by specialized radiopharmaceutical companies in the form of technetium-99m generators worldwide or directly distributed to the local market. Generators, colloquially known as moly cow, are devices designed to provide radiation shields for transportation and to minimize extraction work performed in medical facilities. The typical dose level at 1 meter from the Tc-99m generator is 20-50 Sv/h during transport. This generator output decreases with time and should be changed every week, because half-life 99 Mo is still only 66 hours.
Molybdenum-99 spontaneously decays to an excited state of 99 Tc through beta decay. Over 87% of decay leads to an excited state of 142 keV from Tc-99m. A
? -
electron and
?
e electron antineutrino emitted in the process ( 99 Mo -> 99m Tc
? -
?
e ).
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The electron is easily shielded for transport, and generator 99m Tc is only a small radiation hazard, mostly due to secondary X-rays generated by electrons (also known as Bremsstrahlung ).
In the hospital, 99m Tc formed through decay 99 Mo is chemically extracted from technetium-99m generator. Most commercial generator 99 Mo/ 99m Tc using column chromatography, where 99 Mo in water-soluble molybdate form, MoO 4 2 - is absorbed into acidic alumina (Al 2 O 3 ). When 99 Mo decays, it forms pertechnetate TcO 4 - , which, due to its sole charge, is less tightly bound to alumina. Draw the normal saline solution through the immobilized 99 MoO 4 2 - solute elutes 99m TcO 4 - , resulting in a salt solution containing 99m Tc as soluble sodium salt from pertechnetate. One technetium-99m generator, which holds only a few micrograms of 99 Mo, could potentially diagnose 10,000 patients as it would produce 99m Tc strong for more than a week.
Get started
Technetium out of the generator in the form of pertechnetate ions, TcO 4 - . The state of oxidation of Tc in this compound is 7. It is directly suitable for medical applications only in bone scan (taken by osteoblasts) and some thyroid scans (this is taken at the site of iodine by normal thyroid tissue). In other types of scans that rely on Tc-99m, the reducing agent is added to the pertechnetate solution to bring Tc to 3 or 4 oxidation states. Second, ligands are added to form the coordination complex. Ligands are chosen to have affinity for specific organs to target. For example, the Tc test complex in the oxidation state 3 is able to penetrate the blood-brain barrier and flow through the vessels in the brain to imaging cerebral blood flow. Other ligands include sestamibi for imaging myocardial perfusion and mercapto acetyl triglycine for MAG3 scan to measure renal function.
Medical use
In 1970, Eckelman and Richards presented the first "kit" that contained all the materials needed to release Tc-99m, "milked" from the generator, in chemical form to give to the patient.
Technetium-99m is used in 20 million diagnostic nuclear medical procedures each year. About 85% of diagnostic imaging procedures in nuclear medicine use these isotopes as radioactive tracers. The book Klaus Schwochau Technetium lists 31 radiopharmaceuticals based on 99m Tc for imaging and functional studies of the brain, myocardium, thyroid, lung, liver, gallbladder, kidney, skeleton, blood, and tumors. Depending on the procedure, 99m Tc is tagged (or bound) a pharmacy that transports it to the required location. For example, when 99m Tc is chemically bound to the exametazime (HMPAO), it is able to cross the blood-brain barrier and flow through the vessels in the brain for brain blood flow imaging. This combination is also used to label white blood cells to visualize infection sites. 99m Tc sestamibi is used for imaging myocardial perfusion, which shows how well blood flows through the heart. Imaging to measure renal function was performed by attaching 99m Tc to mercaptoacetyl triglycine (MAG3); this procedure is known as MAG3 scan.
Technetium-99m can be easily detected in the body by medical equipment because it emits gamma rays 140.5 keV (this is about the same wavelength as emitted by conventional X-ray diagnostic equipment), and the half-life of gamma emission is six hours (meaning 94% of it decays to 99 Tc in 24 hours). The "short" physical half-isotope and biological half-day (in terms of human activity and metabolism) allow for a scanning procedure that collects data quickly, but keeps the total exposure of patient radiation low.
Radiation side effects
A diagnostic treatment involving technetium-99m will result in radiation exposure for technicians, patients, and passers-by. The typical amount of technetium given for immunoscintigraphy tests, such as the SPECT test, ranges from 400-1.100 MBq (11 to 30 mCi) (millicurie or mCi; and Mega-Becquerel or MBq) for adults. This dose produces radiation exposure for patients about 10 mSv (1000 mrem), equivalent to about 500 x-ray of chest exposure. This level of radiation exposure carries 1 in 1,000 lifetime risks to develop cancer or leukemia in patients. The risk is higher in younger patients, and lower in older adults. Unlike chest x-rays, radiation sources are present in the patient and will be taken for several days, exposing others to second-hand radiation. A couple who remain on the patient's side during this time may receive a thousandth of a patient's radiation dose in this way.
Short half-life of the isotope allows for a scanning procedure that collects data quickly. Isotopes also have very low energy levels for gamma emitters. Its 140 keV energy makes it safer to use because ionization is considerably reduced compared to other gamma emitters. The gammas energy of 99m Tc is almost identical to the radiation from a commercial diagnostic X-ray machine, although the amount of emitted gammas results in a radiation dose more comparable to X-ray studies such as computed tomography..
Technetium-99m has several features that make it more secure than other isotopes. Gamma decay mode can be easily detected by the camera, allowing the use of smaller amounts. And since technetium-99m has a short half-life, rapid decay into much lower-than-99 tehetium yields relatively low total radiation doses for patients per unit of initial activity after administration, compared with other radioisotopes. In the form given in this medical test (usually pertechnetate), technetium-99m and technetium-99 are eliminated from the body within a few days.
3-D scanning techniques: SPECT
Single photon emission computed tomography (SPECT) is a nuclear medicine imaging technique using gamma rays. It can be used with gamma-emitting isotopes, including Tc-99m. In the use of technetium-99m, radioisotopes are given to the patient and the escape gamma ray occurs in a moving gamma camera that computes and processes the image. To obtain a SPECT image, the gamma camera is rotated around the patient. The projection is obtained at the points specified during the rotation, usually every three to six degrees. In most cases, full 360 Â ° rotation is used to obtain optimal reconstruction. The time required to obtain each projection also varies, but 15-20 seconds is typical. This gives a total scan time of 15-20 minutes.
Technetium-99m radioisotopes are used primarily in bone and brain scans. For bone scans, pertechnetate ions are used directly, since they are taken by osteoblasts that attempt to heal bone injuries, or (in some cases) the reaction of these cells to tumors (either primary or metastatic) in the bone. In brain scanning, Tc-99m is attached to the HMPAO chelating agent to create technetium ( 99m Tc) exametazime, an agent that localizes in the brain according to the blood flow in the area, making it useful for detecting stroke and dementia that decreases brain flow and regional metabolism.
Recently, technetium-99m scintigraphy has been combined with CT coregistration technology to produce SPECT/CT scans. It uses the same radioligands and has the same usability as SPECT scanning, but is able to provide better 3-D localization of high uptake networks, in cases where better resolution is required. An example is the sestamibi parathyroid scan performed using a Tc-99m radioligand sestamibi, and can be performed either in SPECT or SPECT/CT machines.
Bone scan
Nuclear medicine techniques commonly called bone scan usually use Tc-99m. This is not to be confused with "bone density scanning", DEXA, which is a low-exposure X-ray test measuring bone density to look for osteoporosis and other diseases where bone loses mass without rebuilding activity. Nuclear medicine techniques are sensitive to unusual areas of bone formation activity, because radiofarmaka is taken by osteoblast cells that build bones. Therefore this technique is sensitive to fractures and bone reactions to bone tumors, including metastases. For bone scan, the patient is injected with a small amount of radioactive material, such as 700-1,100 MBq (19-30 mCi)
Myocardial perfusion imaging
Myocardial perfusion imaging (MPI) is a form of functional cardiac imaging, used for the diagnosis of ischemic heart disease. The underlying principle is that, under stressful conditions, the ailing myocardium receives less blood flow than the normal myocardium. MPI is one of several types of cardiac stress tests. As a nuclear stress test, the average radiation exposure is 9.4 mSV compared with 2 chest X-Ray displays (0.1 mSV) equivalent to 94 X-Rays Chest.
Some radiopharmaceuticals and radionuclides can be used for this, each providing different information. In myocardial perfusion scan using Tc-99m, radiofarmaka 99m Tc-tetrofosmin (Myoview, GE Healthcare) or 99m Tc-sestamibi (Cardiolite, Bristol-Myers Squibb) is used. After this, myocardial stress is induced, either by exercise or pharmacologically with adenosine, dobutamine or dipyridamole (Persantine), which increases heart rate or by regadenosone (Lexiscan), a vasodilator. (Aminophylline may be used to reverse the effects of dipyridamole and regadenosone). Scanning can be done with a conventional gamma camera, or with SPECT/CT.
Cardiac ventricular
In cardiac ventriculography, radionuclides, usually 99m Tc, injected, and heart are imaged to evaluate the flow through it, to evaluate coronary artery disease, valvular heart disease, congenital heart disease, cardiomyopathy and other heart disorders. As a nuclear stress test, the average radiation exposure is 9.4 mSV compared with 2 chest X-Ray displays (0.1 mSV) equivalent to 94 X-Rays Chest. This exposes the patient to less radiation compared with comparable chest X-ray studies.
Functional brain imagery
Usually the gamma-emitting tracer used in functional brain imaging is 99m Tc-HMPAO (hexamethylpropylene amine oxime, exametazime). Similar trackers 99m Tc-EC can also be used. These molecules are typically distributed to areas of high cerebral blood flow, and act to assess brain metabolism regionally, in an attempt to diagnose and differentiate different causes of dementia. When used with SPECT 3-D techniques, they compete with FDG-PET brain scans and fMRI brain scans as a technique for mapping the regional metabolic rate of brain tissue.
Identify the sentence-node
Radioactive properties 99m Tc can be used to identify the dominant lymph nodes that exhaust cancer, such as breast cancer or malignant melanoma. This is usually done at the time of biopsy or resection. 99m The isosulfan blue dye labeled Tc in intradermal around the site of the biopsy in question. The general location of sentinel nodes is determined by using a hand-held scanner with a gamma-sensor sensor that detects colloidal sulfur labeled technetium-99m previously injected around the site of the biopsy. An incision is then made on top of the highest accumulation of radionuclides, and sentinel nodes are identified in the incision by examination; isosulfan blue dyes will usually stain the dry blue nodes.
Immunoscintigraphy
Immunoscintigraphy combines 99m Tc into monoclonal antibodies, immune system proteins, capable of binding cancer cells. A few hours after the injection, medical equipment is used to detect gamma rays emitted by 99m Tc; Higher concentrations indicate where the tumor is located. This technique is very useful for detecting cancer that is hard to find, as it affects the intestines. This modified antibody is sold by the German company Hoechst (now part of Sanofi-Aventis) under the name "Scintium".
Blood pool pooling
When 99m Tc is combined with lead compounds, it binds red blood cells and can therefore be used to map out circulatory system disorders. This is usually used to detect gastrointestinal bleeding sites.
Pyrophosphate for heart damage
Pyrophosphate ion with 99m Tc embraces calcium deposits in damaged heart muscle, making it useful for measuring damage after a heart attack.
Colloidal sulfur for spleen scan
Colloid sulfur 99m Tc is preyed by the spleen, making it possible to describe the spleen structure.
Diverticulum Meckel
Pertechnetate is actively accumulated and secreted by gastric mucoid mucoid cells, and therefore, technetate (VII) labeled radiolabel with Tc99m is injected into the body when looking for ectopic gastric tissue as found in Meckel's diverticulum with Meckel's Scans.
See also
- Cholescintigraphy
- Technetium isotope
- Temporary equilibrium
Note
References
- Quote
- References
Further reading
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P. Saraswathy, A.C. Dey, S.K. Sarkar, C. Koth, alkar, P. Naskar, G. Arjun, S.S. Arora, A.K.Kohli, V. Meera, V.Venugopal and N.Ramamoorthy (2007). "The 99mTc generator for clinical use based on zirconium molybdate gel and (n, gamma) yields 99 M: Indian experience in the development and deployment of indigenous processing technologies and facilities" (PDF) . Proceedings of the International RERTR Meeting 2007 . CS1 maint: Many names: list of authors (links) - Iturralde, Mario P. (December 1, 1996). "Molybdenum-99 production in South Africa". European Journal of Nuclear Medicine . 23 (12): 1681-1687. doi: 10.1007/BF01249633.
- Hansell, Cristina (July 1, 2008). "Dual Dangers of Nuclear Treatment: Irregular Treatment and Terrorism Risk" (PDF) . The Nonproliferation Review . 15 (2): 185-208. doi: 10.1080/10736700802117270 . Retrieved May 24 2012 .
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