Radioisotopes, also called radionuclides, are usually artificially produced unstable atoms of a naturally occurring element. These isotopes have the same number of electrons and protons as the naturally occurring element, but different number of neutrons. More than 1000 radioisotopes are known to occur. Of these, only about 50 are naturally occurring. Most radioisotopes are produced by bombarding the atoms of the stable, naturally occurring element with fast-moving neutrons produced in a nuclear reactor or particle accelerator.
These isotopes tend to revert to the natural, stable elements at a rate that is specific to each isotope of each element. The rate of conversion of an isotope to its stable elemental composition determines its time in existence and is measured by half-life, the time it takes for half of the radioisotope population to convert.
In a hospital setting, radiopharmaceuticals are typically handled by the nuclear pharmacy or radiopharmacy, involved in the preparation of radioactive materials for diagnosis and/or treatment of specific diseases. In diagnostic applications, radiopharmaceuticals accumulate in specific tissues or cells and emit radiation, which can be collected and processed into images, showing the location of the accumulation in the body, for diagnostic purposes. In therapeutic applications, the high-energy radiation released by radiopharmaceuticals destroys undesired local cells and tissue.
Types of radiation
The unstable nuclei of radioisotopes dissipate energy, in the form of specific types of radiation, as they spontaneously convert to the stable parent isotopes. These radiations are commonly known as alpha, beta, or gamma rays.
1. Alpha radiation is a result of excess energy dissipation by unstable nuclei in the form of alpha particles. The alpha particles have two positive charges and a total mass of four units. This is exemplified by polonium 210Po84 decaying to 206Po82, in a notation where superscript before the element’s symbol represents the atomic mass and the subscript after the element’s symbol represents the atomic number. The alpha particles, being heavy, are ejected at about 1/10th the speed of light and are not very penetrating. They can travel about 1–4 inches in the air.
2. Beta radiation is produced through beta decay of unstable nuclei and can follow either of the three processes: electron emission, positron emission, and electron capture.
• Negative beta decay involves the emission of an energetic electron and an antineutrino (which does not have a resting mass). In the resulting nucleus, a neutron becomes a proton and stays in the nucleus. Thus, the proton number (atomic number) of the resulting nucleus increases by one, while the mass number (total number of protons and neutrons in the nucleus) does not change. For example, this process occurs for tritium (3H) decay to radioactive helium (3He).
• Positive beta decay involves the emission of a positron, similar to an electron in all aspects but with opposite charge, and a neutrino. In the resulting nucleus, a proton converts to a neutron. Thus, the atomic number of the daughter nucleus is one less than the parent, while the atomic mass remains the same.
• Electron capture is a process whereby an orbiting electron combines with a nuclear proton to form a neutron (which remains in the nucleus) and a neutrino (which is emitted). In the resulting nucleus, the atomic number reduces by one, while the atomic mass stays the same.
• Beta decay is usually a slower process compared with alpha or gamma decay. Most beta particles are emitted at the speed of light.
3. Gamma rays are the most penetrating electromagnetic radiation of shortest wavelength and highest energy, just above the X-ray region of the electromagnetic spectrum. Gamma rays can be produced by the decay of the radioactive nuclei or of certain subatomic particles. The mechanism of formation of high-energy gamma ray photons is currently not well understood.
The quantity of radioactive material is measured in terms of activity rather than mass. The amount of radioactivity is typically expressed in the units of Curie (Ci), which is a measure of radioactivity per unit mass of material. The international system of units (SI system) recommends becquerel (Bq) as a unit of radioactivity.
One Bq represents the amount of radiation produced from one disintegration per second (dps). One Ci is 37-billion Bq or 37 GBq. While Ci is the unit of measurement of radioactivity, the absorbed dose of ionizing radiation is expressed in rad, the dose equivalent (when radiation is applied to humans) is expressed in rem, and the exposure to radiation is quantitated in roentgen (R). One rad represents the amount of radiation that releases energy of 100 ergs per gram of matter. Erg is a unit of energy or work that equals 10−7 Joules. Rem is the dosage in rads that causes the same amount of biological injury as 1 rad of X-rays or gamma rays.
In the SI system of units, where Bq is the unit of radioactivity, gray (Gy) is the unit of expression of absorbed dose, Sievert (Sv) is the dose equivalent unit, and exposure is expressed in coulomb per kilogram body weight (C/kg). One rad is 0.01 Gy and one rem is 0.01 Sv.
Radiation exposure can lead to several side effects that can be understood as the impact of radiation on rapidly dividing cells. The following side effects are commonly observed in patients undergoing radiation therapy of cancer:
• Hair loss
• Gastrointestinal irritation becoming evident as nausea, vomiting, diarrhea, and stomach upset
• Low white blood cell count (leucopenia).
• Local side effects such as reddening and itchiness of the skin, if applied
• Oral mucositis, leading to sore mouth or oral ulcers
In addition, the following protection guidelines are recommended for the users:
1. Time: The shorter the time of potential use of a radioactive material, the shorter the duration of exposure. Thus, quick and efficient work with minimal time of exposure of the radioactive material to the ambient laboratory environment is recommended.
2. Distance: The farther a person is from a source of radiation, the lower the dose of radiation exposure. In addition, physical contact with the radioactive material is generally avoided with the use of devices to manipulate or move stored containers of radioactive material.
3. Shielding: Radioisotopes are typically handled in lead containers, since lead absorbs and is impervious to all radiation. X-ray technicians and laboratory personnel wear lead-coated aprons to block potential direct exposure to radiation.
4. Quantity: The amount of radioactive material in the working area and inventory is generally minimized. Multiple procurements of small quantities are preferred over purchasing and storing one large quantity.
Radioactive tracers and diagnosis
Use of radioisotopes as tracers and diagnostic agents depends on the ease of detection of the radiation emitted by the isotope and the ability of the isotopic element to be incorporated into the molecule that is being traced (such as during the biodistribution studies of new drug candidates). As diagnostic agents, radioactive elements are typically adsorbed or incorporated on a carrier. Thus, chemical identity, ability to use during synthesis, and the form of the radioisotopes are important for their applications as tracers and diagnostic agents.
Diagnostic uses of radioisotopes can be exemplified by thyroid function studies using low dose 131I, erythrocyte tagging for identification of type of anemia using 51Cr, and metabolic studies using 14C. The 14C radioisotope detection in breath can be used to detect the presence of ulcer-causing bacteria Helicobacter pylori. There is an increasing preference for the use of nonradioactive methods of analyses, wherever possible, due to the handling risks associated with radioactive isotopes.
Use of radioisotopes as radiation sources for radiotherapy aims to utilize the tissue damage that results from radiation to, for example, reduce the amount of cancerous tissue. Selection of radioisotopes as radiotherapy agents depends mainly on the type and energy of radiation emitted by the isotope and its depth of tissue penetration. Chemical identity and reactivity are of relatively less importance for radiotherapy applications. Radioisotopes used for therapy can be applied to the target tissue either from an external source or on administration to the patient as a drug.
1. External source application of radiation has the advantages of duration and amount of dose titration, with direct observation of the target tissue, and of being able to remove the radiation source—and terminate treatment—at any time. Radioisotopes used for external therapy are exemplified by cobalt (60Co) and cesium (137Cs). They have been used for the treatment of undesired lesions.
2. Internal application, or administration of the radiotherapy agent to the patient, has a limitation that the source of radiation cannot be removed once administered. Therefore, the amount of radioisotope administered to the patient must be carefully controlled. Radioisotopes that have been used for internal therapy include gold (198Au), iridium (192Ir), phosphorus (32P as sodium phosphate), yttrium (90Y), iodine (131I as sodium iodide), and palladium (103P).
• Colloidal gold (198Au) suspensions have been used in the cases of fluid accumulation in the abdomen (peritoneal cavity) or chest (plural cavity), associated with malignant tumors. The colloidal suspension diffuses throughout the fluid and, over time, tends to aggregate at the surface of the cavity.
• Nylon ribbons containing iridium (192Ir) seeds at periodic intervals can be implanted into the interstitial cavity, such as abdominal, for the treatment of tumors. These ribbons are surgically removable.
• Radiophosphorus (32P) can be injected parenterally as a solution of a highly soluble sodium salt. The phosphorus tends to accumulate in rapidly proliferating cells and tissues. Accordingly, it has been used for the treatment of polycythemia vera (too many red blood cells produced by the bone marrow) and chronic granulocytic or myeloid leukemia (too many blood cells produced by the bone marrow). At relatively high doses (1.5–5 mCi), 32P accumulates in the bone marrow and can suppress the production of blood cells.
• Yttrium (90Y) has a strong affinity for chelating agents, which can be used for targeting carriers. Yttrium chelate with pentetic acid or diethylenetriaminepentaacetic acid (DTPA) can be used for localization to the lymphatics, and its chelate with ethylenediaminetetraacetic acid (EDTA) can lead to localization in the bone.
• Iodine (131I), used as a water-soluble salt, sodium iodide, is perhaps the most commonly known radioisotope used for the treatment of goiter, Graves’ disease, and thyroid cancer. Iodine is selectively taken up by the thyroid gland in the neck. The uptake of radioactive iodine can cause localized tissue destruction by radiation produced within the gland. Targeted uptake of 131I by select tissues can be achieved by incorporation into compounds such as metaiodobenzylguanidine (mIBG). The 131I-labeled mIBG is selectively taken up by the adrenal medullary tissues and can be used to treat carcinomas of or metastases from the adrenal medullary glands.
• Radioimmunotherapy is the targeting of radioisotopes to specific cells, tissues, and tumor types by covalent conjugation of a radioisotope to monoclonal antibodies or their antigen-binding fragments. For example, 131I can be conjugated to antibodies by using N-hydroxysuccinimide (NHS) to produce radiolabeled antibodies. Copper isotope, 67Cu, can be conjugated to antibodies by using the chelating agent [6-p-nitrobenzyl]-l,4,8,lltetraazacyclotetradecane-N, N′, N″, N‴ tetraacetate (TETA) for radioimmunotherapy.
Radiation detection equipment
1. Scintillation detector for the detection of gamma-radiation emitting probes. A scintillation probe can be suitably modified to detect the localization of isotopes in the organs of interest. For example, detection of 131I uptake by the thyroid and the uptake of red blood cells labeled with 51Cr by the spleen require appropriately modified gamma scintigraphy equipment.
2. Scintillation counters are typical laboratory equipment used for the detection and measurement of ionizing radiation. These counters can be used to test samples of in vitro testing (such as drug release or dissolution) and in vivo samples after digestion into a homogeneous liquid (such as biodistribution studies).
3. Positron emission tomography (PET) is a functional imaging technique applied in nuclear medicine to measure whole body metabolism. It detects gamma rays emitted by a positron-emitting radionuclide 18F fluorodeoxyglucose that is administered to the patient as a tracer before the procedure. A computerized tomography (CT) X-ray scan is concurrently performed on the patient to construct a three- dimensional (3D) image of the patient, which is then utilized to construct a 3D location of the radioisotope in the body in what is known as the CT-PET scan. This scan can detect regional metabolic activity, as indicated by regional glucose uptake. This scan is commonly used to detect cancer metastases.
4. Geiger counter, also known as the Geiger–Muller counter, is a typical name for a handheld device for measuring ionizing radiation most commonly used by the laboratory safety personnel. It detects ionizing radiation, including alpha particles, beta particles, and gamma rays, using the ionization effect produced by the radiation in a Geiger–Muller tube. The Geiger–Muller tube is filled with an inert, unionized gas (He, Ne, or Ar) at low pressure and is equipped with an anode and a cathode under high voltage (400–600 V).