technetium-99m technetium-99m 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 in the world. technetium-99m, 99mtcthe first technetium-99m generator, 1958.a 99mtc pertechnetate solution isbeing eluted from 99mo molybdatebound to a chromatographic substrategeneralsymbol99mtcnamestechnetium-99m, 99mtc, tc-99mprotons (z)43neutrons (n)56nuclide datahalf-life (t1/2)6.0067 hisotope mass98.9063 daspin1/2−excess energy−87327.195 kevbinding energy8613.603 kevparent isotopes99mo (65.976 h)decay products99tcdecay modesdecay modedecay energy (mev)isomeric transitionγ emission 87.87%98.6%: 0.1405 mev 1.4%: 0.1426isotopes of technetium complete table of nuclides 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 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. 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 37-inch (940 mm) cyclotron of ernest orlando lawrence's radiation laboratory. in 1970 seaborg explained that: we discovered an isotope of great scientific interest, because it decayed by means of an isomeric transition with emission of a line spectrum of electrons coming from an almost completely internally converted gamma ray transition. (...) this was a form of radioactive decay which had never been observed before this time. segrè and i were able to show that this radioactive isotope of the element with the atomic number 43 decayed with a half-life of 6.6 h and that it was the daughter of a 67-h molybdenum parent radioactivity. this chain of decay was later shown to have the mass number 99, and (...) the 6.6-h activity acquired the designation ‘technetium-99m. later in 1940, emilio segrè and chien-shiung wu 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 a technetium injection contained in a shielded syringe 99mtc remained a scientific curiosity until the 1950s when powell richards 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 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 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 (41°14′6.88″n 74°12′50.78″w)). 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, 200,000 ci (7.4×1015 bq) of total fission product radiation were extracted weekly from 20 to 30 reactor bombarded heu capsules, using the so-called "cintichem process." the research facility with its 1961 5-mw pool-type research reactor was later sold to hoffman-laroche and became cintichem inc. in 1980, cintichem, inc. began the production/isolation of 99mo in its reactor, and became the single u.s. producer of 99mo during the 1980s. however, in 1989, cintichem detected an underground leak of radioactive products that led to the reactor shutdown and decommissioning, putting an end to the commercial production of 99mo in the usa. the production of 99mo started in canada in the early 1970s and was shifted to the nru reactor in the mid-1970s. by 1978 the reactor provided technetium-99m in large enough quantities that were processed by aecl's radiochemical division, which was privatized in 1988 as nordion, now mds nordion. in the 1990s a substitution for the aging nru reactor for production of radioisotopes was planned. the multipurpose applied physics lattice experiment (maple) was designed as a dedicated isotope-production facility. initially, two identical maple reactors were to be built at chalk river laboratories, 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) 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 nuclide in an excited (metastable) state that lasts much longer than is typical. the nucleus will eventually relax (i.e., de-excite) to its ground state 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. 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. pure gamma emission is the desirable decay mode for medical imaging because other particles deposit more energy in the patient body (radiation dose) 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 and it is in the middle of the range of half lives for radiopharmaceuticals used for medical imaging. after gamma emission or internal conversion, the resulting ground-state technetium-99 then decays with a half-life of 211,000 years to stable ruthenium-99. this process emits soft beta radiation without a gamma. such low radioactivity from the daughter product(s) is a desirable feature for radiopharmaceuticals. tc 43 99 m → 6 h γ 141 kev tc 43 99 → 211 , 000 y β − 249 kev ru 44 99 ( stable ) ⏞ ruthenium − 99 _tc->_^tc->\overbrace _ru}} ^ production neutron irradiation of uranium-235 targets the parent nuclide of 99mtc, 99mo, is mainly extracted for medical purposes from the fission products created in neutron-irradiated uranium-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. nuclear reactors producing 99mo from 235u targets. the year indicates the date of the first criticality of the reactor. type reactor location target/fuel year large-scale producersnru (decommissioned)canadaheu/leu1957 br2belgiumheu/heu1961 safari-1south africaleu/leu1965 hfrthe netherlandsheu/leu1961 osiris reactorfranceleu/heu1966 regional producersopalaustralialeu/leu2006 mpr rsg-gasindonesialeu/leu1987 ra-3argentinaleu/leu1961 mariapolandheu/heu1974 lvr-15czech republicheu/heu1957 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 "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 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