Radioactive tracer

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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radiotracer, or radioactive label is a synthetic derivative of a natural compound in which one or more atoms have been replaced by a radionuclide (a radioactive atom). 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.

Contents

Radioisotopes of hydrogen, carbon, phosphorus, sulfur, and iodine have been used extensively to trace the path of biochemical reactions. A radioactive tracer can also be used to track the distribution of a substance within a natural system such as a cell or tissue, [1] or as a flow tracer to track fluid flow. Radioactive tracers are also used to determine the location of fractures created by hydraulic fracturing in natural gas production. [2] Radioactive tracers form the basis of a variety of imaging systems, such as, PET scans, SPECT scans and technetium scans. Radiocarbon dating uses the naturally occurring carbon-14 isotope as an isotopic label.

Methodology

Isotopes of a chemical element differ only in the mass number. For example, the isotopes of hydrogen can be written as 1H, 2H and 3H, with the mass number superscripted to the left. When the atomic nucleus of an isotope is unstable, compounds containing this isotope are radioactive. Tritium is an example of a radioactive isotope.

The principle behind the use of radioactive tracers is that an atom in a chemical compound is replaced by another atom, of the same chemical element. The substituting atom, however, is a radioactive isotope. This process is often called radioactive labeling. The power of the technique is due to the fact that radioactive decay is much more energetic than chemical reactions. Therefore, the radioactive isotope can be present in low concentration and its presence detected by sensitive radiation detectors such as Geiger counters and scintillation counters. George de Hevesy won the 1943 Nobel Prize for Chemistry "for his work on the use of isotopes as tracers in the study of chemical processes".

There are two main ways in which radioactive tracers are used

  1. When a labeled chemical compound undergoes chemical reactions one or more of the products will contain the radioactive label. Analysis of what happens to the radioactive isotope provides detailed information on the mechanism of the chemical reaction.
  2. A radioactive compound is introduced into a living organism and the radio-isotope provides a means to construct an image showing the way in which that compound and its reaction products are distributed around the organism.

Production

The commonly used radioisotopes have short half lives and so do not occur in nature in large amounts. They are produced by nuclear reactions. One of the most important processes is absorption of a neutron by an atomic nucleus, in which the mass number of the element concerned increases by 1 for each neutron absorbed. For example,

13C + n → 14C

In this case the atomic mass increases, but the element is unchanged. In other cases the product nucleus is unstable and decays, typically emitting protons, electrons (beta particle) or alpha particles. When a nucleus loses a proton the atomic number decreases by 1. For example,

32S + n → 32P + p

Neutron irradiation is performed in a nuclear reactor. The other main method used to synthesize radioisotopes is proton bombardment. The proton are accelerated to high energy either in a cyclotron or a linear accelerator. [3]

Tracer isotopes

Hydrogen

Tritium (hydrogen-3) is produced by neutron irradiation of 6Li:

6Li + n → 4He + 3H

Tritium has a half-life 4500±8 days (approximately 12.32 years) [4] and it decays by beta decay. The electrons produced have an average energy of 5.7 keV. Because the emitted electrons have relatively low energy, the detection efficiency by scintillation counting is rather low. However, hydrogen atoms are present in all organic compounds, so tritium is frequently used as a tracer in biochemical studies.

Carbon

11C decays by positron emission with a half-life of ca. 20 min. 11C is one of the isotopes often used in positron emission tomography. [3]

14C decays by beta decay, with a half-life of 5730 years. It is continuously produced in the upper atmosphere of the earth, so it occurs at a trace level in the environment. However, it is not practical to use naturally-occurring 14C for tracer studies. Instead it is made by neutron irradiation of the isotope 13C which occurs naturally in carbon at about the 1.1% level. 14C has been used extensively to trace the progress of organic molecules through metabolic pathways. [5]

Nitrogen

13N decays by positron emission with a half-life of 9.97 min. It is produced by the nuclear reaction

1H + 16O → 13N + 4He

13N is used in positron emission tomography (PET scan).

Oxygen

15O decays by positron emission with a half-life of 122 seconds. It is used in positron emission tomography.

Fluorine

18F decays predominantly by β emission, with a half-life of 109.8 min. It is made by proton bombardment of 18O in a cyclotron or linear particle accelerator. It is an important isotope in the radiopharmaceutical industry. For example, it is used to make labeled fluorodeoxyglucose (FDG) for application in PET scans. [3]

Phosphorus

32P is made by neutron bombardment of 32S

32S + n → 32P + p

It decays by beta decay with a half-life of 14.29 days. It is commonly used to study protein phosphorylation by kinases in biochemistry.

33P is made in relatively low yield by neutron bombardment of 31P. It is also a beta-emitter, with a half-life of 25.4 days. Though more expensive than 32P, the emitted electrons are less energetic, permitting better resolution in, for example, DNA sequencing.

Both isotopes are useful for labeling nucleotides and other species that contain a phosphate group.

Sulfur

35S is made by neutron bombardment of 35Cl

35Cl + n → 35S + p

It decays by beta-decay with a half-life of 87.51 days. It is used to label the sulfur-containing amino-acids methionine and cysteine. When a sulfur atom replaces an oxygen atom in a phosphate group on a nucleotide a thiophosphate is produced, so 35S can also be used to trace a phosphate group.

Technetium

99mTc is a very versatile radioisotope, and is the most commonly used radioisotope tracer in medicine. It is easy to produce in a technetium-99m generator, by decay of 99Mo.

99Mo → 99mTc +
e−
 +
ν
e

The molybdenum isotope has a half-life of approximately 66 hours (2.75 days), so the generator has a useful life of about two weeks. Most commercial 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. The pertechnetate is treated with a reducing agent such as Sn2+ and a ligand. Different ligands form coordination complexes which give the technetium enhanced affinity for particular sites in the human body.

99mTc decays by gamma emission, with a half-life: 6.01 hours. The short half-life ensures that the body-concentration of the radioisotope falls effectively to zero in a few days.

Iodine

123I is produced by proton irradiation of 124 Xe. The caesium isotope produced is unstable and decays to 123I. The isotope is usually supplied as the iodide and hypoiodate in dilute sodium hydroxide solution, at high isotopic purity. [6] 123I has also been produced at Oak Ridge National Laboratories by proton bombardment of 123Te. [7]

123I decays by electron capture with a half-life of 13.22 hours. The emitted 159  keV gamma ray is used in single-photon emission computed tomography (SPECT). A 127 keV gamma ray is also emitted.

125I is frequently used in radioimmunoassays because of its relatively long half-life (59 days) and ability to be detected with high sensitivity by gamma counters. [8]

129I is present in the environment as a result of the testing of nuclear weapons in the atmosphere. It was also produced in the Chernobyl and Fukushima disasters. 129I decays with a half-life of 15.7 million years, with low-energy beta and gamma emissions. It is not used as a tracer, though its presence in living organisms, including human beings, can be characterized by measurement of the gamma rays.

Other isotopes

Many other isotopes have been used in specialized radiopharmacological studies. The most widely used is 67Ga for gallium scans. 67Ga is used because, like 99mTc, it is a gamma-ray emitter and various ligands can be attached to the Ga3+ ion, forming a coordination complex which may have selective affinity for particular sites in the human body.

An extensive list of radioactive tracers used in hydraulic fracturing can be found below.

Applications

In metabolism research, tritium and 14C-labeled glucose are commonly used in glucose clamps to measure rates of glucose uptake, fatty acid synthesis, and other metabolic processes. [9] While radioactive tracers are sometimes still used in human studies, stable isotope tracers such as 13C are more commonly used in current human clamp studies. Radioactive tracers are also used to study lipoprotein metabolism in humans and experimental animals. [10]

In medicine, tracers are applied in a number of tests, such as 99mTc in autoradiography and nuclear medicine, including single-photon emission computed tomography (SPECT), positron emission tomography (PET) and scintigraphy. The urea breath test for helicobacter pylori commonly used a dose of 14C labeled urea to detect h. pylori infection. If the labeled urea was metabolized by h. pylori in the stomach, the patient's breath would contain labeled carbon dioxide. In recent years, the use of substances enriched in the non-radioactive isotope 13C has become the preferred method, avoiding patient exposure to radioactivity. [11]

In hydraulic fracturing, radioactive tracer isotopes are injected with hydraulic fracturing fluid to determine the injection profile and location of created fractures. [2] Tracers with different half-lives are used for each stage of hydraulic fracturing. In the United States amounts per injection of radionuclide are listed in the US Nuclear Regulatory Commission (NRC) guidelines. [12] According to the NRC, some of the most commonly used tracers include antimony-124, bromine-82, iodine-125, iodine-131, iridium-192, and scandium-46. [12] A 2003 publication by the International Atomic Energy Agency confirms the frequent use of most of the tracers above, and says that manganese-56, sodium-24, technetium-99m, silver-110m, argon-41, and xenon-133 are also used extensively because they are easily identified and measured. [13]

Related Research Articles

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.

<span class="mw-page-title-main">Beta particle</span> Ionizing radiation

A beta particle, also called beta ray or beta radiation, is a high-energy, high-speed electron or positron emitted by the radioactive decay of an atomic nucleus, known as beta decay. There are two forms of beta decay, β− decay and β+ decay, which produce electrons and positrons, respectively.

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.

Ionizing 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 up to 99% of the speed of light, and the electromagnetic waves are on the high-energy portion of the electromagnetic spectrum.

<span class="mw-page-title-main">Single-photon emission computed tomography</span> Nuclear medicine tomographic imaging technique

Single-photon emission computed tomography is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera, but is able to provide true 3D information. This information is typically presented as cross-sectional slices through the patient, but can be freely reformatted or manipulated as required.

<span class="mw-page-title-main">Positron emission</span> Type of radioactive decay

Positron emission, beta plus decay, or β+ decay is a subtype of radioactive decay called beta decay, in which a proton inside a radionuclide nucleus is converted into a neutron while releasing a positron and an electron neutrino. Positron emission is mediated by the weak force. The positron is a type of beta particle (β+), the other beta particle being the electron (β−) emitted from the β− decay of a nucleus.

<span class="mw-page-title-main">Neutron emission</span> Type of radioactive decay

Neutron emission is a mode of radioactive decay in which one or more neutrons are ejected from a nucleus. It occurs in the most neutron-rich/proton-deficient nuclides, and also from excited states of other nuclides as in photoneutron emission and beta-delayed neutron emission. As only a neutron is lost by this process the number of protons remains unchanged, and an atom does not become an atom of a different element, but a different isotope of the same element.

<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">Radiochemistry</span> Chemistry of radioactive materials

Radiochemistry is the chemistry of radioactive materials, where radioactive isotopes of elements are used to study the properties and chemical reactions of non-radioactive isotopes. Much of radiochemistry deals with the use of radioactivity to study ordinary chemical reactions. This is very different from radiation chemistry where the radiation levels are kept too low to influence the chemistry.

<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.

Natural nitrogen (7N) consists of two stable isotopes: the vast majority (99.6%) of naturally occurring nitrogen is nitrogen-14, with the remainder being nitrogen-15. Thirteen radioisotopes are also known, with atomic masses ranging from 9 to 23, along with three nuclear isomers. All of these radioisotopes are short-lived, the longest-lived being nitrogen-13 with a half-life of 9.965(4) min. All of the others have half-lives below 7.15 seconds, with most of these being below 620 milliseconds. Most of the isotopes with atomic mass numbers below 14 decay to isotopes of carbon, while most of the isotopes with masses above 15 decay to isotopes of oxygen. The shortest-lived known isotope is nitrogen-10, with a half-life of 143(36) yoctoseconds, though the half-life of nitrogen-9 has not been measured exactly.

Various radionuclides emit beta particles, high-speed electrons or positrons, through radioactive decay of their atomic nucleus. These can be used in a range of different industrial, scientific, and medical applications. This article lists some common beta-emitting radionuclides of technological importance, and their properties.

<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.

Iodine-123 (123I) is a radioactive isotope of iodine used in nuclear medicine imaging, including single-photon emission computed tomography (SPECT) or SPECT/CT exams. The isotope's half-life is 13.2232 hours; the decay by electron capture to tellurium-123 emits gamma radiation with a predominant energy of 159 keV. In medical applications, the radiation is detected by a gamma camera. The isotope is typically applied as iodide-123, the anionic form.

<span class="mw-page-title-main">Radioactivity in the life sciences</span>

Radioactivity is generally used in life sciences for highly sensitive and direct measurements of biological phenomena, and for visualizing the location of biomolecules radiolabelled with a radioisotope.

<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.

A germanium-68/gallium-68 generator is a device used to extract the positron-emitting isotope 68Ga of gallium from a source of decaying germanium-68. The parent isotope 68Ge has a half-life of 271 days and can be easily utilized for in-hospital production of generator produced 68Ga. Its decay product gallium-68 is extracted and used for certain positron emission tomography nuclear medicine diagnostic procedures, where the radioisotope's relatively short half-life and emission of positrons for creation of 3-dimensional PET scans, are useful.

Emission computed tomography (ECT) is a type of tomography involving radioactive or emissions. Types include positron emission tomography (PET) and Single-photon emission computed tomography (SPECT).

<span class="mw-page-title-main">Radiopharmaceutical</span> Pharmaceutical drug which emits radiation, used as a diagnostic or therapeutic agent

Radiopharmaceuticals, or medicinal radiocompounds, are a group of pharmaceutical drugs containing radioactive isotopes. Radiopharmaceuticals can be used as diagnostic and therapeutic agents. Radiopharmaceuticals emit radiation themselves, which is different from contrast media which absorb or alter external electromagnetism or ultrasound. Radiopharmacology is the branch of pharmacology that specializes in these agents.

References

  1. ↑ Rennie MJ (November 1999). "An introduction to the use of tracers in nutrition and metabolism". The Proceedings of the Nutrition Society. 58 (4): 935–44. doi: 10.1017/S002966519900124X . PMID   10817161.
  2. 1 2 Reis, John C. (1976). Environmental Control in Petroleum Engineering. Gulf Professional Publishers.
  3. 1 2 3 Fowler J. S. and Wolf A. P. (1982) The synthesis of carbon-11, fluorine-18 and nitrogen-13 labeled radiotracers for biomedical applications. Nucl. Sci. Ser. Natl Acad. Sci. Natl Res. Council Monogr. 1982.
  4. ↑ Lucas LL, Unterweger MP (2000). "Comprehensive Review and Critical Evaluation of the Half-Life of Tritium" (PDF). Journal of Research of the National Institute of Standards and Technology. 105 (4): 541–9. doi:10.6028/jres.105.043. PMC   4877155 . PMID   27551621. Archived from the original (PDF) on 2011-10-17.
  5. ↑ Kim SH, Kelly PB, Clifford AJ (April 2010). "Calculating radiation exposures during use of (14)C-labeled nutrients, food components, and biopharmaceuticals to quantify metabolic behavior in humans". Journal of Agricultural and Food Chemistry. 58 (8): 4632–7. doi:10.1021/jf100113c. PMC   2857889 . PMID   20349979.
  6. ↑ I-123 fact sheet [ permanent dead link ]
  7. ↑ Hupf HB, Eldridge JS, Beaver JE (April 1968). "Production of iodine-123 for medical applications". The International Journal of Applied Radiation and Isotopes. 19 (4): 345–51. doi:10.1016/0020-708X(68)90178-6. PMID   5650883.
  8. ↑ Gilby ED, Jeffcoate SL, Edwards R (July 1973). "125-Iodine tracers for steroid radioimmunoassay". The Journal of Endocrinology. 58 (1): xx. PMID   4578967.
  9. ↑ Kraegen EW, Jenkins AB, Storlien LH, Chisholm DJ (1990). "Tracer studies of in vivo insulin action and glucose metabolism in individual peripheral tissues". Hormone and Metabolic Research. Supplement Series. 24: 41–8. PMID   2272625.
  10. ↑ Magkos F, Sidossis LS (September 2004). "Measuring very low density lipoprotein-triglyceride kinetics in man in vivo: how different the various methods really are". Current Opinion in Clinical Nutrition and Metabolic Care. 7 (5): 547–55. doi:10.1097/00075197-200409000-00007. PMID   15295275. S2CID   26085364.
  11. ↑ Peeters M (1998). "Urea breath test: a diagnostic tool in the management of Helicobacter pylori-related gastrointestinal diseases". Acta Gastro-Enterologica Belgica. 61 (3): 332–5. PMID   9795467.
  12. 1 2 Whitten JE, Courtemanche SR, Jones AR, Penrod RE, Fogl DB, Division of Industrial and Medical Nuclear Safety, Office of Nuclear Material Safety and Safeguards (June 2000). "Consolidated Guidance About Materials Licenses: Program-Specific Guidance About Well Logging, Tracer, and Field Flood Study Licenses (NUREG-1556, Volume 14)". US Nuclear Regulatory Commission. Retrieved 19 April 2012. labeled Frac Sand...Sc-46, Br-82, Ag-110m, Sb-124, Ir-192
  13. ↑ Radiation Protection and the Management of Radioactive Waste in the Oil and Gas Industry (PDF) (Report). International Atomic Energy Agency. 2003. pp. 39–40. Retrieved 20 May 2012. Beta emitters, including 3H and 14C, may be used when it is feasible to use sampling techniques to detect the presence of the radiotracer, or when changes in activity concentration can be used as indicators of the properties of interest in the system. Gamma emitters, such as 46Sc, 140La, 56Mn, 24Na, 124Sb, 192Ir, 99Tcm, 131I, 110Agm, 41Ar and 133Xe are used extensively because of the ease with which they can be identified and measured. ... In order to aid the detection of any spillage of solutions of the 'soft' beta emitters, they are sometimes spiked with a short half-life gamma emitter such as 82Br...
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