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Application of Radiopharmaceuticals

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Applications of Radiopharmaceuticals

Name: Lew Chien Ai

Introduction

Radiopharmaceuticals are formulations containing radioisotopes, which are use internally for therapeutic and diagnostic purposes. Radiopharmaceuticals have modernized the medical field by their ability to provide static as well as dynamic images of internal organs in a noninvasive manner as well as by offering efficacious therapy of certain diseases.
Radioisotopes are extensively used in medicine for diagnosis, either in vivo or in vitro, for therapeutics and also for investigation purposes. Nuclear medicine (NM) studies in vivo are used to detect minimal amounts of radiopharmaceuticals in organs (the morphology) and their course over time (the function), resulting from physico-chemical interactions of the tracers within the body, in the sequence of specific physiological processes. In vitro applications of radioisotopes have become a most important tool in biochemical analysis. Therapeutic uses of radioisotopes cover from external gamma-ray sources in teleradiotherapy to direct cell irradiation in metabolic therapy.
Radioisotopes can be use in medicine in four different ways. They are:
1. Radioactive tracers for diagnostic purposes
2. Radiation source in therapy
3. Research and
4. Sterilization
The radioisotope therapy has been available to those disease conditions in which extensive cellular malfunction exists.

Diagnostic radiopharmaceuticals are used to derive detailed description of the morphology and dynamic functioning of the various internal organs of the body. The radiopharmaceutical accumulated in an organ of interest emit gamma radiation which are used for imaging of the organs with the help of an external imaging device called gamma camera.

The following are examples of radiopharmaceuticals, which are in practice worldwide for various diagnostic purposes * Abscess and infection—Gallium Citrate Ga 67, Indium In 111 Oxyquinoline * Appendicitis—Technetium (99m Tc) Fanolesomab * Biliary tract blockage—Technetium Tc 99m Disofenin, Technetium Tc 99m Lidofenin, Technetium Tc 99m Mebrofenin * Blood volume studies—Radioiodinated Albumin, Sodium Chromate Cr 51 * Blood vessel diseases—Sodium Pertechnetate Tc 99m * Blood vessel diseases of the brain—Ammonia N 13, Iofetamine I 123, Technetium Tc 99m Bicisate, Technetium Tc 99m Exametazime, Xenon Xe 133 * Bone diseases—Sodium Fluoride F 18, Technetium Tc 99m Medronate, Technetium Tc 99m Oxidronate, Technetium Tc 99m Pyrophosphate, Technetium Tc 99m (Pyro- and trimeta-) Phosphates * Parathyroid diseases; parathyroid cancer—Technetium Tc 99m Sestamibi, Thallous Chloride Tl 201

Therapeutic Radiopharmaceuticals are radiolabeled molecules designed to deliver therapeutic doses of ionizing radiation to specific diseased sites. Therapeutic applications of radiopharmaceuticals have emerged from the concept that certain radionuclides possessing particulate emission such as alpha and beta radiations or low-energy low-range electrons (Auger electrons) possess the ability to destroy diseased tissues.
Contrary to the usual requirement that intravenous injections be true solutions, some radiopharmaceuticals are deliberately particulate to achieve site-specific localization of radioactivity in the body. These specialized dosage forms permit imaging of, for example, the principal organs of the reticuloendothelial system (liver, spleen, and bone marrow) with radiolabeled colloidal particles, the cardiac blood pool with radiolabeled red blood cells, and lung perfusion with albumin aggregates.
Radioisotopes may be used internally or externally. If the radioisotopes are used externally or as implants in sealed capsules in a tissue, the dose could be terminated by removal of the sources. If they are given internally as unsealed source, the dose cannot be stopped by removal of the source. The total dose in therapeutic applications may be calculated on the basis of effective half- life of the isotope, concentration of the isotope and the type and energy of radiation emitted.
Studies have been carried out for radioactive isotopes as tracers. Modern knowledge of many biochemical processes has been the cause of such elaborate studies146 C and 31H are most commonly used radionuclides for this purpose.
Sterilization – Excellent use is being made of the radiation constantly available from some strong radiation sources for sterilizing pharmaceuticals in their final packed containers and surgical instruments in hospitals. The radiation does not destroy or harm most pharmaceuticals. No heat or chemicals get involve.
Thermolabile substance such as vitamins, hormones, antibiotics etc can be safely sterilized 6027Co or Cesium-37 may be used for sterilizing surgical instruments. It also finds use for sterilizing pharmaceuticals.

Effects

The most significant effect of the interaction of radiation with tissues is radiolysis of water. Initially, absorption of energy by water molecules leads to the ejection of electrons. The resulting positively charged ion dissociates to produce a hydrogen ion and a hydroxide free radical. Electrons react with further water molecules to produce hydroxide ions and hydrogen free radicals. It is the production of these highly reactive free radicals, either electron-acceptors or electron donors, which induces subsequent damage.

At the molecular level, free radicals can initiate strand breakage in DNA, or disruption in the structure of protein molecules. An outward manifestation of this molecular damage can occur at different times after the event, depending on the extent of the initial exposure and the nature of the molecular damage. For instance, if double-strand breakage in a DNA molecule occurs, there is little chance of repair. Cell death may occur, or cell abnormality and mutation may be transmitted to daughter cells, leading to possible malignancy. Abnormality in germinal cells may lead to offspring inheriting abnormal characteristics
Interaction of X-rays or gamma rays with matter causes ionization, resulting in the production of negatively charged electrons and positively charged ions. Electrons will travel short distances, and can produce further ionization.
Positive ions can bring about chemical changes, which are the prime cause of radiation injury.

Quality Assurance

Radiopharmaceuticals are generally expected to conform to specifications under the following ways: * Radionuclide concentration * Radiochemical purity * Chemical purity * Sterility * Apyrogenicity * Absence of foreign particulate matter * Particle size (if appropriate) * pH * Biological distribution *
Some of these parameters may be measured directly on products prior to use. However, one of the characteristics of many diagnostic radiopharmaceuticals is the inclusion of short-lived radionuclides.
These radioactive elements often have half-lives measured in hours, minutes or even seconds, making meaningful testing of the end products impractical. Most diagnostic radiopharmaceuticals contain the radionuclide technetium-99m, an artificial radioactive element with a half-life of six hours. In these circumstances, great emphasis must be placed on adoption of an effective programme of quality assurance.…...

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