Technetium-99m generator

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Five modern technetium-99m generators Five99mTechnetiumGenerators.jpg
Five modern technetium-99m generators
The first technetium-99m generator, unshielded, 1958. A Tc-99m pertechnetate solution is being eluted from Mo-99 molybdate bound to a chromatographic substrate First technetium-99m generator - 1958.jpg
The first technetium-99m generator, unshielded, 1958. A Tc-99m pertechnetate solution is being eluted from Mo-99 molybdate bound to a chromatographic substrate

A technetium-99m generator, or colloquially a technetium cow or moly cow, is a device used to extract the metastable isotope 99mTc of technetium from a decaying sample of molybdenum-99. 99Mo has a half-life of 66 hours [1] and can be easily transported over long distances to hospitals where its decay product technetium-99m (with a half-life of only 6 hours, inconvenient for transport) is extracted and used for a variety of nuclear medicine diagnostic procedures, where its short half-life is very useful.

Contents

Parent isotope source

99Mo can be obtained by the neutron activation (n,γ reaction) of 98Mo in a high-neutron-flux reactor. However, the most frequently used method is through fission of uranium-235 in a nuclear reactor. While most reactors currently engaged in 99Mo production use highly enriched uranium-235 targets, proliferation concerns have prompted some producers to transition to low-enriched uranium targets. [2] The target is irradiated with neutrons to form 99Mo as a fission product (with 6.1% yield). [3] Molybdenum-99 is then separated from unreacted uranium and other fission products in a hot cell. [4]

Generator invention and history

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. [5] 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 tellurium-132, its 3.2-days parent, produced in the Brookhaven Graphite Research Reactor. [6] 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. [7] [8] It was not until 1960 that Richards became the first to suggest the idea of using technetium as a medical tracer. [9] [10] [11] [12]

Generator function and mechanism

Technetium-99m's short half-life of 6 hours makes long-term storage impossible. Transport of 99mTc from the limited number of production sites to radiopharmacies (for manufacture of specific radiopharmaceuticals) and other end users would be complicated by the need to significantly overproduce to have sufficient remaining activity after long journeys. Instead, the longer-lived parent nuclide 99Mo can be supplied to radiopharmacies in a generator, after its extraction from the neutron-irradiated uranium targets and its purification in dedicated processing facilities. [13] Radiopharmacies may be hospital-based or stand-alone facilities, and in many cases will subsequently distribute 99mTc radiopharmaceuticals to regional nuclear medicine departments. Development in direct production of 99mTc, without first producing the parent 99Mo, precludes the use of generators; however, this is uncommon and relies on suitable production facilities close to radiopharmacies. [14]

Production

Generators provide radiation shielding for transport and to minimize the extraction work done at the medical facility. A typical dose rate at 1 metre from 99mTc generator is 20–50 μSv/h during transport. [15]

These generators' output declines with time and must be replaced weekly, since the half-life of 99Mo is still only 66 hours. Since the half-life of the parent nuclide (99Mo) is much longer than that of the daughter nuclide (99mTc), 50% of equilibrium activity is reached within one daughter half-life, 75% within two daughter half-lives. Hence, removing the daughter nuclide (elution process) from the generator ("milking" the cow) is reasonably done as often as every 6 hours in a 99Mo/99mTc generator. [16]

Separation

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. Pouring normal saline solution through the column of immobilized 99Mo elutes the soluble 99mTc, resulting in a saline solution containing the 99mTc as pertechnetate, with sodium as the counterion.

The solution of sodium pertechnetate may then be added in an appropriate concentration to the pharmaceutical kit to be used, or sodium pertechnetate can be used directly without pharmaceutical tagging for specific procedures requiring only the 99mTcO4− as the primary radiopharmaceutical. A large percentage of the 99mTc generated by a 99Mo/99mTc generator is produced in the first 3 parent half-lives, or approximately one week. Hence, clinical nuclear medicine units purchase at least one such generator per week or order several in a staggered fashion. [17]

Isomeric ratio

When the generator is left unused, 99Mo decays to 99mTc, which in turn decays to 99Tc. The half-life of 99Tc is far longer than its metastable isomer, so the ratio of 99Tc to 99mTc increases over time. Both isomers are carried out by the elution process and react equally well with the ligand, but the 99Tc is an impurity useless to imaging (and cannot be separated).

The generator is washed of 99Tc and 99mTc at the end of the manufacturing process of the generator, but the ratio of 99Tc to 99mTc then builds up again during transport or any other period when the generator is left unused. The first few elutions will have reduced effectiveness because of this high ratio. [18]

Related Research Articles

<span class="mw-page-title-main">Technetium</span> Chemical element with atomic number 43 (Tc)

Technetium is a chemical element; it has symbol Tc and atomic number 43. It is the lightest element whose isotopes are all radioactive. Technetium and promethium are the only radioactive elements whose neighbours in the sense of atomic number are both stable. All available technetium is produced as a synthetic element. Naturally occurring technetium is a spontaneous fission product in uranium ore and thorium ore, or the product of neutron capture in molybdenum ores. This silvery gray, crystalline transition metal lies between manganese and rhenium in group 7 of the periodic table, and its chemical properties are intermediate between those of both adjacent elements. The most common naturally occurring isotope is 99Tc, in traces only.

A radionuclide (radioactive nuclide, radioisotope or radioactive isotope) is a nuclide that has excess numbers of either neutrons or protons, giving it excess nuclear energy, and making it unstable. This excess energy can be used in one of three ways: emitted from the nucleus as gamma radiation; transferred to one of its electrons to release it as a conversion electron; or used to create and emit a new particle (alpha particle or beta particle) from the nucleus. During those processes, the radionuclide is said to undergo radioactive decay. These emissions are considered ionizing radiation because they are energetic enough to liberate an electron from another atom. The radioactive decay can produce a stable nuclide or will sometimes produce a new unstable radionuclide which may undergo further decay. Radioactive decay is a random process at the level of single atoms: it is impossible to predict when one particular atom will decay. However, for a collection of atoms of a single nuclide the decay rate, and thus the half-life (t1/2) for that collection, can be calculated from their measured decay constants. The range of the half-lives of radioactive atoms has no known limits and spans a time range of over 55 orders of magnitude.

A synthetic radioisotope is a radionuclide that is not found in nature: no natural process or mechanism exists which produces it, or it is so unstable that it decays away in a very short period of time. Frédéric Joliot-Curie and Irène Joliot-Curie were the first to produce a synthetic radioisotope in the 20th century. Examples include technetium-99 and promethium-146. Many of these are found in, and harvested from, spent nuclear fuel assemblies. Some must be manufactured in particle accelerators.

A radioactive tracer, radiotracer, or radioactive label is a synthetic derivative of a natural compound in which one or more atoms have been replaced by a radionuclide. By virtue of its radioactive decay, it can be used to explore the mechanism of chemical reactions by tracing the path that the radioisotope follows from reactants to products. Radiolabeling or radiotracing is thus the radioactive form of isotopic labeling. In biological contexts, experiments that use radioisotope tracers are sometimes called radioisotope feeding experiments.

<span class="mw-page-title-main">Nuclear fission product</span> Atoms or particles produced by nuclear fission

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 of heat energy, and gamma rays. The two smaller nuclei are the fission products..

<span class="mw-page-title-main">Radiopharmacology</span> Pharmacologic study of radiated medical compounds

Radiopharmacology is radiochemistry applied to medicine and thus the pharmacology of radiopharmaceuticals. Radiopharmaceuticals are used in the field of nuclear medicine as radioactive tracers in medical imaging and in therapy for many diseases. Many radiopharmaceuticals use technetium-99m (Tc-99m) which has many useful properties as a gamma-emitting tracer nuclide. In the book Technetium a total of 31 different radiopharmaceuticals based on Tc-99m are listed for imaging and functional studies of the brain, myocardium, thyroid, lungs, liver, gallbladder, kidneys, skeleton, blood and tumors.

<span class="mw-page-title-main">Pertechnetate</span> Chemical compound or ion

The pertechnetate ion is an oxyanion with the chemical formula TcO−
4. It is often used as a convenient water-soluble source of isotopes of the radioactive element technetium (Tc). In particular it is used to carry the 99mTc isotope which is commonly used in nuclear medicine in several nuclear scanning procedures.

Uranium (92U) is a naturally occurring radioactive element (radioelement) with no stable isotopes. It has two primordial isotopes, uranium-238 and uranium-235, that have long half-lives and are found in appreciable quantity in Earth's crust. The decay product uranium-234 is also found. Other isotopes such as uranium-233 have been produced in breeder reactors. In addition to isotopes found in nature or nuclear reactors, many isotopes with far shorter half-lives have been produced, ranging from 214U to 242U. The standard atomic weight of natural uranium is 238.02891(3).

<span class="mw-page-title-main">Isotopes of iodine</span>

There are 40 known isotopes of iodine (53I) from 108I to 147I; all undergo radioactive decay except 127I, which is stable. Iodine is thus a monoisotopic element.

Technetium (43Tc) is one of the two elements with Z < 83 that have no stable isotopes; the other such element is promethium. It is primarily artificial, with only trace quantities existing in nature produced by spontaneous fission or neutron capture by molybdenum. The first isotopes to be synthesized were 97Tc and 99Tc in 1936, the first artificial element to be produced. The most stable radioisotopes are 97Tc, 98Tc, and 99Tc.

Molybdenum (42Mo) has 39 known isotopes, ranging in atomic mass from 81 to 119, as well as four metastable nuclear isomers. Seven isotopes occur naturally, with atomic masses of 92, 94, 95, 96, 97, 98, and 100. All unstable isotopes of molybdenum decay into isotopes of zirconium, niobium, technetium, and ruthenium.

Naturally occurring zirconium (40Zr) is composed of four stable isotopes (of which one may in the future be found radioactive), and one very long-lived radioisotope (96Zr), a primordial nuclide that decays via double beta decay with an observed half-life of 2.0×1019 years; it can also undergo single beta decay, which is not yet observed, but the theoretically predicted value of t1/2 is 2.4×1020 years. The second most stable radioisotope is 93Zr, which has a half-life of 1.53 million years. Thirty other radioisotopes have been observed. All have half-lives less than a day except for 95Zr (64.02 days), 88Zr (83.4 days), and 89Zr (78.41 hours). The primary decay mode is electron capture for isotopes lighter than 92Zr, and the primary mode for heavier isotopes is beta decay.

Plutonium (94Pu) is an artificial element, except for trace quantities resulting from neutron capture by uranium, and thus a standard atomic weight cannot be given. Like all artificial elements, it has no stable isotopes. It was synthesized long before being found in nature, the first isotope synthesized being plutonium-238 in 1940. Twenty-one plutonium radioisotopes have been characterized. The most stable are plutonium-244 with a half-life of 80.8 million years; plutonium-242 with a half-life of 373,300 years; and plutonium-239 with a half-life of 24,110 years; and plutonium-240 with a half-life of 6,560 years. This element also has eight meta states; all have half-lives of less than one second.

<span class="mw-page-title-main">Fission products (by element)</span> Breakdown of nuclear fission results

This page discusses each of the main elements in the mixture of fission products produced by nuclear fission of the common nuclear fuels uranium and plutonium. The isotopes are listed by element, in order by atomic number.

<span class="mw-page-title-main">Technetium-99m</span> Metastable nuclear isomer of technetium-99

Technetium-99m (99mTc) is a metastable nuclear isomer of technetium-99, 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.

<span class="mw-page-title-main">Technetium-99</span> Radioactive isotope produced by fission of uranium

Technetium-99 (99Tc) is an isotope of technetium which decays with a half-life of 211,000 years to stable ruthenium-99, emitting beta particles, but no gamma rays. It is the most significant long-lived fission product of uranium fission, producing the largest fraction of the total long-lived radiation emissions of nuclear waste. Technetium-99 has a fission product yield of 6.0507% for thermal neutron fission of uranium-235.

Long-lived fission products (LLFPs) are radioactive materials with a long half-life produced by nuclear fission of uranium and plutonium. Because of their persistent radiotoxicity, it is necessary to isolate them from humans and the biosphere and to confine them in nuclear waste repositories for geological periods of time. The focus of this article is radioisotopes (radionuclides) generated by fission reactors.

<span class="mw-page-title-main">Nuclear transmutation</span> Conversion of an atom from one element to another

Nuclear transmutation is the conversion of one chemical element or an isotope into another chemical element. Nuclear transmutation occurs in any process where the number of protons or neutrons in the nucleus of an atom is changed.

Phoenix, formerly known as Phoenix Nuclear Labs, is a company specializing in neutron generator technology located in Monona, Wisconsin, United States. Founded in 2005, the company develops nuclear and particle accelerator technologies for application in medicine, defense and energy. Phoenix has held contracts with the U.S. Army, the U.S. Department of Energy, the U.S. Department of Defense and the U.S. Air Force. Phoenix developed a proprietary gas target neutron generator technology and has designed and built a number of particle accelerator-related technologies.

References

  1. ↑ R. Nave. "Technetium-99m". HyperPhysics. Georgia State University.
  2. ↑ The National Research Council. Medical Isotope Production Without Highly Enriched Uranium (Report). Retrieved 20 November 2012.
  3. ↑ "Archived copy" (PDF). Archived from the original (PDF) on 24 May 2009. Retrieved 2 August 2008.{{cite web}}: CS1 maint: archived copy as title (link)
  4. ↑ Snelgrove L, Hofman GL, Wiencek TC, Wu CT, Vandegrift GF, Aase S, Buchholz BA, Dong DJ, Leonard RA, Srinivasan B (18–21 September 1994). Development and Processing Of LEU Targets for Mo-99 Production—Overview of the ANL Program. 1995 International Meeting on Reduced Enrichment for Research and Test Reactors. Paris. OSTI   146775.
  5. ↑ Gasparini, Allison (24 October 2018). "Celebrating the 60th Anniversary of Technetium-99m". Brookhaven National Laboratory.
  6. ↑ "Brookhaven Graphite Research Reactor". bnl.gov. Archived from the original on 2 April 2013. Retrieved 3 May 2012.
  7. ↑ Richards, Powell (1989). Technetium-99m: The Early Days. Vol. BNL-43197 CONF-8909193-1. New York: Brookhaven National Laboratory. OSTI   5612212.
  8. ↑ Tucker, W.D.; Greene, M.W.; Weiss, A.J.; Murrenhoff, A. (1958). "Methods of preparation of some carrier-free radioisotopes involving sorption on alumina". Transactions American Nuclear Society. 1: 160–161.
  9. ↑ Richards, Powell (1960). "A survey of the production at Brookhaven National Laboratory of radioisotopes for medical research". VII Rassegna Internazionale Elettronica e Nucleare Roma: 223–244.
  10. ↑ "The Technetium-99m Generator". Bnl.gov. Archived from the original on 2 April 2013.
  11. ↑ Richards, P.; Tucker, W.D.; Srivastava, S.C. (October 1982). "Technetium-99m: an historical perspective". The International Journal of Applied Radiation and Isotopes. 33 (10): 793–9. doi:10.1016/0020-708X(82)90120-X. PMID   6759417.
  12. ↑ Stang, Louis G.; Richards, Powell (1964). "Tailoring the isotope to the need". Nucleonics. 22 (1). ISSN   0096-6207.
  13. ↑ Dilworth, Jonathan R.; Parrott, Suzanne J. (1998). "The biomedical chemistry of technetium and rhenium". Chemical Society Reviews. 27: 43–55. doi:10.1039/a827043z.
  14. ↑ Boschi, Alessandra; Martini, Petra; Pasquali, Micol; Uccelli, Licia (2 September 2017). "Recent achievements in Tc-99m radiopharmaceutical direct production by medical cyclotrons". Drug Development and Industrial Pharmacy. 43 (9): 1402–1412. doi:10.1080/03639045.2017.1323911. PMID   28443689. S2CID   21121327.
  15. ↑ Shaw, Ken B. (Spring 1985). "Worker Exposures: How Much in the UK?" (PDF). IAEA Bulletin. Archived from the original (PDF) on 5 September 2011. Retrieved 19 May 2012.
  16. ↑ Brant, William E.; Helms, Clyde (2012). Fundamentals of Diagnostic Radiology. Lippincott Williams & Wilkins. p. 1240. ISBN   9781451171396.
  17. ↑ Hamilton, David I. (2004). Diagnostic Nuclear Medicine: A Physics Perspective. Springer Science & Business Media. p. 28. ISBN   9783540006909.
  18. ↑ Moore, P.W. (April 1984). "Technetium-99 in generator systems" (PDF). Journal of Nuclear Medicine. 25 (4): 499–502. PMID   6100549 . Retrieved 11 May 2012.
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