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A radioactive tracer, radiotracer, or radioactive label is a chemical compound in which one or more atoms have been replaced by a radionuclide so by virtue of its radioactive decay it can be used to explore the mechanism of chemical reactions by tracing the path that the radioisotope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, use of radioisotope tracers are sometimes called radioisotope feeding experiments. Radioisotopes of
hydrogen Hydrogen is the chemical element with the symbol H and atomic number 1. Hydrogen is the lightest element. At standard conditions hydrogen is a gas of diatomic molecules having the formula . It is colorless, odorless, tasteless, non-to ...
, 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, 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.Reis, John C. (1976). ''Environmental Control in Petroleum Engineering.'' Gulf Professional Publishers. Radioactive tracers form the basis of a variety of imaging systems, such as,
PET scan Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flo ...
s,
SPECT scan Single-photon emission computed tomography (SPECT, or less commonly, SPET) is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera (that is, ...
s and technetium scans. Radiocarbon dating uses the naturally occurring carbon-14 isotope as an isotopic label.


Methodology

Isotope Isotopes are two or more types of atoms that have the same atomic number (number of protons in their nuclei) and position in the periodic table (and hence belong to the same chemical element), and that differ in nucleon numbers ( mass num ...
s of a chemical element differ only in the mass number. For example, the isotopes of
hydrogen Hydrogen is the chemical element with the symbol H and atomic number 1. Hydrogen is the lightest element. At standard conditions hydrogen is a gas of diatomic molecules having the formula . It is colorless, odorless, tasteless, non-to ...
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 # 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. # 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 + n14C 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 + n32P + 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.


Tracer isotopes


Hydrogen

Tritium (hydrogen-3) is produced by neutron irradiation of 6Li: : 6Li + n4He + 3H Tritium has a
half-life Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable ...
days (approximately 12.32 years) 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.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. 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.


Nitrogen

13N decays by positron emission with a half-life of 9.97 min. It is produced by the nuclear reaction : 1H + 16O13N + 4He 13N is used in positron emission tomography (PET scan).


Oxygen

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


Fluorine

18F decays predominately 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.


Phosphorus

32P is made by neutron bombardment of 32S : 32S + n32P + 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 + n35S + 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 Thiophosphates (or phosphorothioates, PS) are chemical compounds and anions with the general chemical formula (''x'' = 0, 1, 2, or 3) and related derivatives where organic groups are attached to one or more O or S. Thiophosphates feature tetrahed ...
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 + + 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. 123I has also been produced at Oak Ridge National Laboratories by proton bombardment of 123Te. 123I decays by
electron capture Electron capture (K-electron capture, also K-capture, or L-electron capture, L-capture) is a process in which the proton-rich nucleus of an electrically neutral atom absorbs an inner atomic electron, usually from the K or L electron shells. ...
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. 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 Chernobyl ( , ; russian: Чернобыль, ) or Chornobyl ( uk, Чорнобиль, ) is a partially abandoned city in the Chernobyl Exclusion Zone, situated in the Vyshhorod Raion of northern Kyiv Oblast, Ukraine. Chernobyl is about n ...
and Fukushima disasters. 129I decays with a
half-life Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable ...
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 scan A gallium scan is a type of nuclear medicine test that uses either a gallium-67 (67Ga) or gallium-68 (68Ga) radiopharmaceutical to obtain images of a specific type of tissue, or disease state of tissue. Gallium salts like gallium citrate and galli ...
s. 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.


Application

In metabolism research, tritium and 14C-labeled glucose are commonly used in glucose clamps to measure rates of glucose uptake,
fatty acid synthesis In biochemistry, fatty acid synthesis is the creation of fatty acids from acetyl-CoA and NADPH through the action of enzymes called fatty acid synthases. This process takes place in the cytoplasm of the cell. Most of the acetyl-CoA which is co ...
, and other metabolic processes. 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. In medicine, tracers are applied in a number of tests, such as 99mTc in autoradiography and
nuclear medicine Nuclear medicine or nucleology is a medical specialty involving the application of radioactive substances in the diagnosis and treatment of disease. Nuclear imaging, in a sense, is " radiology done inside out" because it records radiation emi ...
, including single-photon emission computed tomography (SPECT), positron emission tomography (PET) and
scintigraphy Scintigraphy (from Latin ''scintilla'', "spark"), also known as a gamma scan, is a diagnostic test in nuclear medicine, where radioisotopes attached to drugs that travel to a specific organ or tissue ( radiopharmaceuticals) are taken internally an ...
. 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. In hydraulic fracturing, radioactive tracer isotopes are injected with hydraulic fracturing fluid to determine the injection profile and location of created fractures. 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. According to the NRC, some of the most commonly used tracers include antimony-124, bromine-82, iodine-125,
iodine-131 Iodine-131 (131I, I-131) is an important radioisotope of iodine discovered by Glenn Seaborg and John Livingood in 1938 at the University of California, Berkeley. It has a radioactive decay half-life of about eight days. It is associated with n ...
, iridium-192, and scandium-46. A 2003 publication by the International Atomic Energy Agency confirms the frequent use of most of the tracers above, and says that
manganese-56 Naturally occurring manganese (25Mn) is composed of one stable isotope, 55Mn. 25 radioisotopes have been characterized, with the most stable being 53Mn with a half-life of 3.7 million years, 54Mn with a half-life of 312.3 days, and 52Mn with a hal ...
, sodium-24,
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 medica ...
, silver-110m,
argon-41 Argon (18Ar) has 26 known isotopes, from 29Ar to 54Ar and 1 isomer (32mAr), of which three are stable (36Ar, 38Ar, and 40Ar). On the Earth, 40Ar makes up 99.6% of natural argon. The longest-lived radioactive isotopes are 39Ar with a half-life of ...
, and xenon-133 are also used extensively because they are easily identified and measured.


References


External links


National Isotope Development Center
U.S. Government resources for radioisotopes - production, distribution, and information
Isotope Development & Production for Research and Applications (IDPRA)
U.S. Department of Energy program sponsoring isotope production and production research and development {{DEFAULTSORT:Radioactive Tracer Radiobiology Radiology Radiopharmaceuticals Radioactivity Biochemistry methods Medicinal radiochemistry