Radiopharmaceuticals

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Chapter: Pharmaceutical Drugs and Dosage: Radiopharmaceuticals

Radioisotopes, also called radionuclides, are usually artificially produced unstable atoms of a naturally occurring element.


Radiopharmaceuticals

Introduction

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 radioiso-topes are produced by bombarding the atoms of the stable, naturally occur-ring element with fast-moving neutrons produced in a nuclear reactor or particle accelerator. These isotopes tend to revert to the natural, stable ele-ments 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 radio-active materials for diagnosis and/or treatment of specific diseases. In diag-nostic 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 pur-poses. 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 iso-topes. 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 sub-script 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 result-ing nucleus increases by one, while the mass number (total num-ber 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 neu-trino. 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 com-bines 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. Characteristic features of these types of radiations emitted by the radioisotopes are summarized in Table 13.1.

Units of radioactivity

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.

Table 13.1 Characteristic features of different types of radiation emitted by radioisotopes


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 safety

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

Generally, doses higher than 30 μCi are administered in a hospital setting to ensure adequate safety monitoring.

Avoiding unintended exposure to radiation in a laboratory setting is a key function of the organizational environmental, health, and safety (EHS) organizations. These are done through careful inventory control, engineer-ing controls when handling radioactive materials (such as the use of fume hoods), and proper storage and disposal of radioactive material and con-taminated waste. In addition, the following protection guidelines are rec-ommended 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.

Note that temperature and pressure are not included in the list of radiation safety considerations. In other words, handling a radioactive compound under refrigerated conditions does not provide any lower exposure to radi-ation than handling the same compound at the room temperature. The decay rate of radionuclides is insensitive to temperature and pressure under normal usual laboratory operating conditions.

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