Radiotracer Technique Pdf
Marti Buday
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radiotracer, or radioactive label is a synthetic derivative of a natural compound in which one or more atoms have been replaced by a radionuclide (a radioactive atom).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.
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.
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".
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,
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,
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]
Tritium has a half-life 45008 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.
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]
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]
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.
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.
123I is produced by proton irradiation of 124Xe. 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]
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.
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.
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]
Nuclear medicine is a medical specialty that uses radioactive tracers (radiopharmaceuticals) to assess bodily functions and to diagnose and treat disease. Specially designed cameras allow doctors to track the path of these radioactive tracers. Single Photon Emission Computed Tomography or SPECT and Positron Emission Tomography or PET scans are the two most common imaging modalities in nuclear medicine.
For most diagnostic studies in nuclear medicine, the radioactive tracer is administered to a patient by intravenous injection. However a radioactive tracer may also be administered by inhalation, by oral ingestion, or by direct injection into an organ. The mode of tracer administration will depend on the disease process that is to be studied.
PET scans also use radiopharmaceuticals to create three-dimensional images. The main difference between SPECT and PET scans is the type of radiotracers used. While SPECT scans measure gamma rays, the decay of the radiotracers used with PET scans produce small particles called positrons. A positron is a particle with roughly the same mass as an electron but oppositely charged. These react with electrons in the body and when these two particles combine they annihilate each other. This annihilation produces a small amount of energy in the form of two photons that shoot off in opposite directions. The detectors in the PET scanner measure these photons and use this information to create images of internal organs.
SPECT scans are primarily used to diagnose and track the progression of heart disease, such as blocked coronary arteries. There are also radiotracers to detect disorders in bone, gall bladder disease and intestinal bleeding. SPECT agents have recently become available for aiding in the diagnosis of Parkinson's disease in the brain, and distinguishing this malady from other anatomically-related movement disorders and dementias.
The major purpose of PET scans is to detect cancer and monitor its progression, response to treatment, and to detect metastases. Glucose utilization depends on the intensity of cellular and tissue activity so it is greatly increased in rapidly dividing cancer cells. In fact, the degree of aggressiveness for most cancers is roughly paralleled by their rate of glucose utilization. In the last 15 years, slightly modified radiolabeled glucose molecules (F-18 labeled deoxyglucose or FDG) have been shown to be the best available tracer for detecting cancer and its metastatic spread in the body.
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