Aradioactive tracer,radiotracer, orradioactive label is asynthetic derivative of anatural compound in which one or more atoms have been replaced by aradionuclide (a radioactive atom). By virtue of itsradioactive 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 orradiotracing is thus the radioactive form ofisotopic labeling. In biological contexts, experiments that use radioisotope tracers are sometimes calledradioisotope feeding experiments.
Radioisotopes ofhydrogen,carbon,phosphorus,sulfur, andiodine have been used extensively to trace the path ofbiochemical reactions. A radioactive tracer can also be used to track the distribution of a substance within a natural system such as acell ortissue,[1] or as aflow tracer to trackfluid flow. Radioactive tracers are also used to determine the location of fractures created byhydraulic fracturing in natural gas production.[2] Radioactive tracers form the basis of a variety of imaging systems, such as,PET scans,SPECT scans andtechnetium scans.Radiocarbon dating uses the naturally occurringcarbon-14 isotope as anisotopic label.
In radiopharmaceutical sciences some misuse of established scientific terms exist. Therefore an international “Working Group on Nomenclature in Radiopharmaceutical Chemistry and Related Areas” was formed in 2015 by the Society of Radiopharmaceutical Sciences (SRS). Their goal was to clarify terminology and to establish a standardized nomenclature through global consensus, ensuring consistency and accuracy within the discipline.[3]
Isotopes of achemical element differ only in the mass number. For example, the isotopes ofhydrogen can be written as1H,2H and3H, with the mass number superscripted to the left. When theatomic nucleus of an isotope is unstable, compounds containing this isotope areradioactive.Tritium is an example of a radioactive isotope.
The principle behind the use of radioactive tracers is that anatom in achemical 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 sensitiveradiation detectors such asGeiger counters andscintillation counters.George de Hevesy won the 1943Nobel 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
The commonly used radioisotopes have shorthalf lives and so do not occur in nature in large amounts. They are produced bynuclear 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,
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) oralpha particles. When a nucleus loses a proton theatomic number decreases by 1. For example,
Neutron irradiation is performed in anuclear reactor. The other main method used to synthesize radioisotopes is proton bombardment. The proton are accelerated to high energy either in acyclotron or alinear accelerator.[4]
Tritium (hydrogen-3) is produced by neutron irradiation of6Li:
Tritium has ahalf-life4500±8 days (approximately 12.32 years)[5] and it decays bybeta decay. Theelectrons 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 inbiochemical studies.
11C decays bypositron emission with a half-life of ca. 20 min.11C is one of the isotopes often used inpositron emission tomography.[4]
14C decays bybeta 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-occurring14C for tracer studies. Instead it is made by neutron irradiation of the isotope13C 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.[6]
13N decays bypositron emission with a half-life of 9.97 min. It is produced by the nuclear reaction
13N is used inpositron emission tomography (PET scan).
15O decays by positron emission with a half-life of 122 seconds. It is used in positron emission tomography.
18F decays predominantly by β emission, with a half-life of 109.8 min. It is made by proton bombardment of18O in a cyclotron orlinear particle accelerator. It is an important isotope in theradiopharmaceutical industry. For example, it is used to make labeledfluorodeoxyglucose (FDG) for application in PET scans.[4]
32P is made by neutron bombardment of32S
It decays by beta decay with a half-life of 14.29 days. It is commonly used to study protein phosphorylation bykinases in biochemistry.
33P is made in relatively low yield by neutron bombardment of31P. It is also a beta-emitter, with a half-life of 25.4 days. Though more expensive than32P, the emitted electrons are less energetic, permitting better resolution in, for example, DNA sequencing.
Both isotopes are useful for labelingnucleotides and other species that contain aphosphate group.
35S is made by neutron bombardment of35Cl
It decays by beta-decay with a half-life of 87.51 days. It is used to label the sulfur-containingamino-acidsmethionine andcysteine. When a sulfur atom replaces an oxygen atom in aphosphate group on anucleotide athiophosphate is produced, so35S can also be used to trace a phosphate group.
99mTc is a very versatile radioisotope, and is the most commonly used radioisotope tracer in medicine. It is easy to produce in atechnetium-99m generator, by decay of99Mo.
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 commercial99mTc generators usecolumn chromatography, in which99Mo in the form of molybdate, MoO42− is adsorbed onto acid alumina (Al2O3). When the99Mo decays it formspertechnetate TcO4−, which because of its single charge is less tightly bound to the alumina. Pulling normal saline solution through the column of immobilized99Mo elutes the soluble99mTc, resulting in a saline solution containing the99mTc as the dissolved sodium salt of the pertechnetate. The pertechnetate is treated with areducing agent such asSn2+ and aligand. Different ligands formcoordination 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.
123I is produced by proton irradiation of124Xe. Thecaesium isotope produced is unstable and decays to123I. The isotope is usually supplied as the iodide and hypoiodate in dilute sodium hydroxide solution, at high isotopic purity.[7]123I has also been produced at Oak Ridge National Laboratories by proton bombardment of123Te.[8]
123I decays byelectron capture with a half-life of 13.22 hours. The emitted 159 keVgamma ray is used insingle-photon emission computed tomography (SPECT). A 127 keV gamma ray is also emitted.
125I is frequently used inradioimmunoassays because of its relatively long half-life (59 days) and ability to be detected with high sensitivity by gamma counters.[9]
129I is present in the environment as a result of the testing ofnuclear weapons in the atmosphere. It was also produced in theChernobyl andFukushima disasters.129I decays with ahalf-life of 15.7 million years, with low-energybeta andgamma 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.
Many other isotopes have been used in specialized radiopharmacological studies. The most widely used is67Ga forgallium scans.67Ga is used because, like99mTc, it is a gamma-ray emitter and various ligands can be attached to the Ga3+ ion, forming acoordination 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.
Inmetabolism research, tritium and14C-labeled glucose are commonly used inglucose clamps to measure rates ofglucose uptake,fatty acid synthesis, and other metabolic processes.[10] While radioactive tracers are sometimes still used in human studies,stable isotope tracers such as13C are more commonly used in current human clamp studies. Radioactive tracers are also used to studylipoprotein metabolism in humans and experimental animals.[11]
Inmedicine, tracers are applied in a number of tests, such as99mTc inautoradiography andnuclear medicine, includingsingle-photon emission computed tomography (SPECT), positron emission tomography (PET) andscintigraphy. Theurea breath test forhelicobacter pylori commonly used a dose of14C 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 isotope13C has become the preferred method, avoiding patient exposure to radioactivity.[12]
Inhydraulic 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 USNuclear Regulatory Commission (NRC) guidelines.[13] According to the NRC, some of the most commonly used tracers includeantimony-124,bromine-82,iodine-125,iodine-131,iridium-192, andscandium-46.[13] A 2003 publication by theInternational Atomic Energy Agency confirms the frequent use of most of the tracers above, and says thatmanganese-56,sodium-24,technetium-99m,silver-110m,argon-41, andxenon-133 are also used extensively because they are easily identified and measured.[14]
labeled Frac Sand...Sc-46, Br-82, Ag-110m, Sb-124, Ir-192
Beta emitters, including3H and14C, 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 as46Sc,140La,56Mn,24Na,124Sb,192Ir,99Tcm,131I,110Agm,41Ar and133Xe 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 as82Br...