Nuclear medicine

Editor-in-Chief: Thomas F. Heston, MD, PhD

Overview
Nuclear medicine is a branch of medicine and medical imaging that uses the nuclear properties of matter in diagnosis and therapy. More specifically, nuclear medicine is a part of molecular imaging because it produces images that reflect biological processes that take place at the cellular and subcellular level. Nuclear medicine is the medical specialty dealing with the diagnostic and therapeutic use of unsealed radioactivity.

Background
Nuclear medicine procedures use pharmaceuticals that have been labeled with radionuclides (radiopharmaceuticals). In diagnosis, radioactive substances are administered to patients and the radiation emitted is detected. The diagnostic tests involve the formation of an image using a gamma camera or positron emission tomography, invented by Hal O. Anger, and sometimes called an Anger gamma camera. Imaging may also be referred to as radionuclide imaging or nuclear scintigraphy. Other diagnostic tests use probes to acquire measurements from parts of the body, or counters for the measurement of samples taken from the patient.

In therapy, radionuclides are administered to treat disease or provide palliative pain relief. For example, administration of Iodine-131 is often used for the treatment of thyrotoxicosis and thyroid cancer. Phosphorus-32 was formerly used in treatment of polycythemia vera. Those treatments rely on the killing of cells by high radiation exposure, as compared to diagnostics in which the exposure is kept as low as reasonably achievable (ALARA policy) so as to reduce the chance of creating a cancer.

Nuclear medicine differs from most other imaging modalities in that the tests primarily show the physiological function of the system being investigated as opposed to traditional anatomical imaging such as CT or MRI. In some centers, the nuclear medicine images can be superimposed, using software or hybrid cameras, on images from modalities such as CT or MRI to highlight which part of the body the radiopharmaceutical is concentrated in. This practice is often referred to as image fusion or co-registration.

Nuclear medicine diagnostic tests are usually provided by a dedicated department within a hospital and may include facilities for the preparation of radiopharmaceuticals. The specific name of a department can vary from hospital to hospital, with the most common names being the nuclear medicine department and the radioisotope department.

About two thirds of the world's supply of medical isotopes are produced at the Chalk River Laboratories in Chalk River, Ontario, Canada. The Canadian Nuclear Safety Commission ordered the reactor to be shut down on November 18, 2007 to facilitate repairs after safety concerns. The repairs took longer than expected and in December 2007 a critical shortage of medical isotopes occurred. The Canadian government passed emergency legislation, allowing the reactor to re-start on 16 December 2007, and production of medical isotopes to continue.[1]

The Chalk River reactor is used to irradiate materials with neutrons which are produced in great quantity during the fission of the U-235, which neutrons change the nucleus of the irradiated material by adding a neutron. For example, the second most commonly used radionuclide is Tc-99m, following the most commonly used radionuclide, F-18 (which is produced by accelerator bombardment of O-18 with protons. The O-18 constitutes about 0.20% of ordinary oxygen (mostly O-16), from which it is extracted; see FDG).

In a reactor, molybdenum-98 (Mo-98) is irradiated to become Mo-99, which is then removed from the reactor and shipped to radiopharmaceutical houses all over North America. The Mo-99 radioactively beta decays with a half-life of 2.7 days, turning initially into Tc-99m, which is then extracted (milked) from a "Moly cow" (see technetium-99m generator). The Tc-99m then further decays, while inside a patient, releasing a gamma photon which is detected by the gamma camera. It decays to its ground state of Tc-99, which is relatively non-radioactive compared to Tc-99m.

Diagnostic testing
Diagnostic tests in nuclear medicine exploit the way that the body handles substances differently when there is disease or pathology present. The radionuclide introduced into the body is often chemically bound to a complex that acts characteristically within the body; this is commonly known as a tracer. In the presence of disease, a tracer will often be distributed around the body and/or processed differently. For example, the ligand methylene-diphosphonate (MDP) can be preferentially taken up by bone. By chemically attaching technetium-99m to MDP, radioactivity can be transported and attached to bone via the hydroxyapatite for imaging. Any increased physiological function, such as due to a fracture in the bone, will usually mean increased concentration of the tracer. This often results in the appearance of a 'hot-spot' which is a focal increase in radio-accumulation, or a general increase in radio-accumulation throughout the physiological system. Some disease processes result in the exclusion of a tracer, resulting in the appearance of a 'cold-spot'. Many tracer complexes have been developed in order to image or treat many different organs, glands, and physiological processes. The types of tests can be split into two broad groups: in-vivo and in-vitro:

Types of studies
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
 * Thallium-201
 * Gallium-67
 * Fluorine-18
 * Indium-111

The most commonly used gaseous/aerosol radionuclides are:
 * Xenon-133
 * Krypton-81m
 * Technetium-99m Technegas
 * Technetium-99m DTPA

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 collection of parallel slices form a slice-stack, a three-dimensional representation of the distribution of radionuclide in the patient.

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 dose
A patient undergoing a nuclear medicine procedure will receive a radiation dose. Under present international guidelines it is assumed that any radiation dose, however small, presents a risk. This is controversial, with growing recognition that there may be a threshold below which radiation exposure is harmless, or possibly even beneficial (the principle of hormesis). The radiation doses delivered to a patient in a nuclear medicine investigation present a very small risk of inducing cancer. In this respect it is similar to the risk from X-ray investigations except that the dose is delivered internally rather than from an external source such as an X-ray machine.

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 (Rad 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.