NUCLEAR MEDICINE

Nuclear medicine is a branch of medical imaging that involves the use of radioactive isotopes in the diagnosis and treatment of disease. This imaging may also be referred to as radionuclide imaging or nuclear scintigraphy. The procedures use pharmaceuticals that have been labeled with radionuclides (radiopharmaceuticals). The radionuclides used in nuclear medicine are produced in nuclear reactors or particle accelerator (cyclotrons). In diagnosis, radiopharmaceuticals are administered to patients and the radiation emitted is measured using a gamma camera. The radiation from the radiopharmaceutical makes it possible to radiograph the distribution of the medicinal product throughout the body. The radiation is usually very low, lower than the level of radiation from X-ray investigations.

History
Nuclear medicine began as a medical specialty area for diagnosis and treatment of disease in the late 1950s and early 1960s.However, long before that in the early 1800s scientists such as Jhon Dalton and Amedeo Avogadro were proposing theories on atomic and molecular structure that would serve as the basis for later research and eventually the discovery of radioactivity by A.H.Becquerel in 1896.

Its origins stem from many scientific discoveries, most notably the discovery of x-rays in 1895 and the discovery of "artificial radioactivity" in 1934. The first clinical use of "artificial radioactivity" was carried out in 1937 for the treatment of a patient with leukemia at the University of California at Berkeley.
A landmark event for nuclear medicine occurred in 1946 when a thyroid cancer patient's treatment with radioactive iodine led to complete disappearance of the patient's cancer. This has been considered by some as the true beginning of nuclear medicine. Wide-spread clinical use of nuclear medicine, started in the early 1950s as its use increased to measure the function of the thyroid and to diagnose thyroid disease and for the treatment of patients with hyperthyroidism.

In the mid-sixties and the years that followed, the growth of nuclear medicine as a specialty discipline was phenomenal. The use of nuclear medicine as a specialty discipline began to see exciting growth with significant advances in nuclear medicine technology. The 1970s brought the visualisation of most other organs of the body with nuclear medicine, including liver and spleen scanning, brain tumour localisation, and studies of the gastrointestinal tract.The 1980s saw the use of radio-pharmaceuticals for such critical diagnoses as heart disease and the development of digital computers to add additional power to the technique.

Today, very complex imaging and computer systems are used with these different radioactive components, not only to image and threat disease, but also to provide functional and quantitative analysis of many body system. Nuclear medicine has found a unique niche in the medical imaging field by virtue of its functional imaging capacity.


Physical Principles of Nuclear Medicine

The atomic number describes the number of protons in the nucleus. For a neutral atom this is also the number of electrons outside the nucleus. Subtracting the atomic number from the atomic mass number gives the number of neutrons in the nucleus.
Isotopes are atoms of the same element (i.e., they have the same number of protons, or the same atomic number) which have a different number of neutrons in the nucleus. Isotopes of an element have similar chemical properties. Radioactive isotopes are called radioisotopes. Most of the elements in the periodic table have several isotopes, found in varying proportions for any given element. The average atomic mass of an element takes into account the relative proportions of its isotopes found in nature.

A nuclear binding force holds the nucleus of the atom together. The nuclear mass defect, a slightly lower mass of the nucleus compared to the sum of the masses of its constituent matter, is due to the nuclear binding energy holding the nucleus together. The mass defect can be used to calculate the nuclear binding energy, with E = mc2. The average binding energy per nucleon is a measure of nuclear stability. The higher the average binding energy, the more stable the nucleus.
The Bohr model of the atom described the electrons as orbiting in discrete, precisely defined circular orbits. Electrons can only occupy certain allowed orbitals. For an electron to occupy an allowed orbit, a certain amount of energy must be available.Each orbit is assigned a quantum number, with the lowest quantum numbers being assigned to those orbitals closest to the nucleus. Only a specified maximum number of electrons can occupy an orbital. Under normal circumstances, electrons occupy the lowest energy level orbitals closest to the nucleus. By absorbing additional energy, electrons can be promoted to higher orbitals, and release that energy when they return back to lower energy levels.

Photons are used to describe the wave-particle duality of light. The energy of a photon depends upon its frequency. This helps to explain the photoelectric effect; only photons having a sufficiently high energy are capable of dislodging an electron from the illuminated surface. E = hv where E is the photon energy in J, v is the photon frequency in Hz, and h is Planck's constant, 6.626 x 10-34 J/Hz.Quantum theory offers a mathematical model to help explain the nature of the atom.Quantum theory describes a region surrounding the nucleus which has the highest probability of locating an electron. These orbital "clouds" have some unusual and interesting shapes.

Radioactive decay is the process in which an unstable atomic nucleus spontaneously loses energy by emitting ionizing particles and radiation. These emissions are collectively called ionizing radiations. Depending on how the nucleus loses this excess energy either a lower energy atom of the same form will result, or a completely different nucleus and atom can be formed. The most common types of radiation are called alpha, beta, and gamma radiation, but there are several other varieties of radioactive decay.Radioactive decay rates are normally stated in terms of their half-lives, and the half-life of a given nuclear species is related to its radiation risk. The different types of radioactivity lead to different decay paths which transmute the nuclei into other chemical elements. Examining the amounts of the decay products makes possible radioactive dating.

There are quite a few naturally occurring radionuclides. Any nuclide with an atomic number greater than 83 is radioactive. An atom's atomic number is simply the total number of protons found in the nucleus. There are also many naturally occurring radionuclides with lower atomic numbers.While some radionuclides occur naturally in the environment, there is another class of "man-made" or artificial radionuclides. Artificial radionuclides are generally produced in a cyclotron or some other particle accelerator, in which stable nucleus bombarded by specific particles (neutrons, protons, electrons or some combination of these). By doing so, the nucleus of starting material unstable, and this nucleus will then try to become stable by emitting radioactivity.

Nuclear Pharmacy (radiopharmaceuticals)

Nuclear Pharmacy involves the preparation of radioactive materials for use in nuclear medicine procedures. Radionuclides are combined with other chemical compounds or pharmaceuticals to form radiopharmaceuticals. Radiopharmaceuticals are administered to patients and the radiation emitted can localize to specific organs or cellular receptors. The external detectors (gamma cameras) capture and form images from the radiation emitted by the radiopharmaceuticals.

The concept of nuclear pharmacy was first described in 1960 by Captain William H. Briner while at the National Institutes of Health (NIH) in Bethesda, Maryland. Along with Mr. Briner, John E. Christian, who was a professor in the School of Pharmacy at Purdue University, had written articles and contributed in other ways to set the stage of nuclear pharmacy. William Briner started the NIH Radiopharmacy in 1958. He also brought about principles and procedures important to the assurance of quality radiopharmaceuticals. Christian developed the first formal lecture and laboratory courses in the United States for teaching the basic principles of radioisotope applications. John Christian and William Briner were both active on key national committees responsible for the development, regulation and utilization of radiopharmaceuticals.

In the mid 1970s a petition was formed requesting the formation of a Section on Nuclear Pharmacy in the Academy of General Practice, currently called the Academy of Pharmacy Practice and Management. On April 23, 1975, the petition was finally approved by the American Pharmacists Association (APhA) Board of Trustees. Nuclear pharmacy thus became a new area in pharmacy.

The most commonly used isotope in nuclear medicine is Technetium-99m that is readily and continuously available from a generator system. This generator system uses molybdenum-99 as the ‘parent.”Molybdenum-99 can be the product of either U-235 fission in a nuclear rector or neutron radiation of Mo-98 in reactor. Molybdenum-99 has a half life of 66.7 hours and decay (82%) to a daughter product known as metastable technetium (Tc 99m). The most commonly used radioisotope in nuclear medicine F-18, is not produced in any nuclear reactor, but rather in a circular acclererator called a cyclotron. The cyclotron is used to accelerate protons to bombard the stable heavy isotope of oxygen O-18. The O-18 constitutes about 0.20% of ordinary oxygen (mostly O-16), from which it is extracted. A typical nuclear medicine study involves administration of a radionuclide into the body by intravenous injection in liquid or aggregate form, ingestion while combined with food, inhalation as a gas or aerosol, or rarely, injection of a radionuclide that has undergone micro-encapsulation. Some studies require the labeling of a patient's own blood cells with a radionuclide (leukocyte scintigraphy and red blood cell scintigraphy). Most diagnostic radionuclides emit gamma rays, while the cell-damaging properties of beta particles are used in therapeutic applications. Refined radionuclides for use in nuclear medicine are derived from fission or fusion processes in nuclear reactors, which produce radioisotopes with longer half-lives, or cyclotrons, which produce radioisotopes with shorter half-lives, or take advantage of natural decay processes in dedicated generators, i.e. molybdenum/technetium or strontium/rubidium.

The most commonly used intravenous radionuclides are: Technetium-99m, Iodine-123 and 131, Gallium-67, Thallium-201, Fluorine-18 Fluorodeoxyglucose, and Indium-111 Labeled Leukocytes. The most commonly used gaseous/aerosol radionuclides are: Krypton-81m, Xenon-133, Technetium-99m Technegas, and Technetium-99m DTPA
The generator forms the radionuclide that is retained on an internal column until the generator is "milked". When "milking" the generator, sodium chloride is passed over the column, which removes the radioactive material. The eluate is then collected in a shielded evacuated vial. After performing quality assurance tests on the eluate, it can be used in the preparation of the final radiopharmaceutical products.

Clinical Nuclear Medicine

Nuclear medicine procedures are generally divided into three basic categories : in Vivo, in Vitro/radioimmunoassay (RIA) and radionuclide therapy procedures.
In Vivo Procedures
The term in vivo is defined as “ within the living body.” This category includes all diagnostic nuclear medicine imaging procedures. Since diagnostic imaging procedures are based on the distribution of radiopharmaceuticals”within the body,”they are classified as in vivoexaminations.
There are wide variety of in vivo/diagnostic imaging examination performed in nuclear medicine. These examination can be described based on the imaging method used : Static, whole body dynamic, Single Photon Emission Computed Tomography (SPECT), and Positrion Emission Tomography (PET).

In Vitro Procedures

In vitro is defined as “ withn a glass; observable n a test tube; in an artificial environment.” This category is use to describe those nuclear medicine examination that require an evaluation or analysis of radioactive samples taken from the human body. Results from these examination are usually a specific quantitative value rather than a diagnostic image.

Radioimmunoassay

Radioimmunoassay (RIA) procedures are performed on body samples such as whole blood, serum, spinal fluid, and urine. Spesific target structures or ligands, such as antibodies or metabolically active drugs, are labeled with a radioactive tracer to determine their levels. Examples radioimmunoassay include thyroid hormone values (T3-Triiodothyronine, T4-Thyroxine, or TSH-thyroid stimulating hormone), drug levels (digoxin, digitoxin, methyltrexate, theophylline, aminophylin, cyclosporine), and vitamins (Vitamin B12, folic acid). Level of these particular hormones, drugs, and vitamins are determined by counting these labeled samples in a specialized scintillation counter. These assay are very sensitive and specific and are used to determine minute levels (µG/dl) of a wide range of ligands.

Analysis

The end result of the nuclear medicine imaging process is a "dataset" comprising one or more images. In multi-image datasets the array of images may represent a time sequence (ie. cine or movie) often called a "dynamic" dataset, a cardiac gated time sequence, or a spatial sequence where the gamma-camera is moved relative to the patient. SPECT (single photon emission computed tomography) is the process by which images acquired from a rotating gamma-camera are reconstructed to produce an image of a "slice" through the patient at a particular position. A distribution of radionuclide in the patient.

Many of the procedures being performed in nuclear medicine department require some form of quantitative analysis, which provides physicians with numeric results based on function. Specialized software allows nuclear medicine computers to collect, process, and analysis functional information information obtained from nuclear medicine imaging system. Cardiac ejection fraction are one of the more common quantitative results provided from nuclear medicine procedures.

The nuclear medicine computer may require millions of lines of source code to provide quantitative analysis packages for each of the specific imaging techniques available in nuclear medicine. Time sequences can be further analysed using kinetic models such as multi-compartment models or a Patlak plot.

Radiation Safety

The radiation protection requirements in nuclear medicine are unique and different from general radiation safety measures used for diagnostic x-ray. Most of the radionuclides used in nuclear medicine are in either liquid or gaseous form. Because of the nature of radioactive decay, these liquids or gases continually emit radiation (unlike diagnostic x –ray which can turn on and off mechanically) and therefore require special precautions.

The radiation dose from a nuclear medicine investigation is expressed as an effective dose with units of sieverts (usually given in millisieverts, mSv). The effective dose resulting from an investigation is influenced by the amount of radioactivity administered in megabecquerels (MBq), the physical properties of the radiopharmaceutical used, its distribution in the body and its rate of clearance from the body.

Effective doses can range from 6 μSv (0.006 mSv) for a 3 MBq chromium-51 EDTA measurement of glomerular filtration rate to 37 mSv for a 150 MBq thallium-201 non-specific tumour imaging procedure. The common bone scan with 600 MBq of technetium-99m-MDP has an effective dose of 3 mSv (1).
Formerly, units of measurement were the curie (Ci), being 3.7E10 Bq, and also 1.0 grams of Radium (Ra-226); the rad (radiation absorbed dose), now replaced by the gray; and the rem (Röntgen equivalent man), now replaced with the sievert. The rad and rem are essentially equivalent for almost all nuclear medicine procedures, and only alpha radiation will produce a higher Rem or Sv value, due to its much higher Relative Biological Effectiveness (RBE). Alpha emitters are nowadays rarely used in nuclear medicine, but were used extensively before the advent of nuclear reactor and accelerator produced radioisotopes. The concepts involved in radiation exposure to humans is covered by the field of Health Physics.

In order to provide protection while handling radioactive material, most compounding is done behind leaded glass shielding and using leaded glass syringe shields and lead containers to hold the radioactive material. Lead is an excellent shielding material that serves to protect the nuclear worker from the radioactive emissions.