Nuclear Medicine

Nuclear Medicine

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Nuclear medicine involves the injection of a radiopharmaceutical (radioactive drug) into a patient for either the diagnosis or treatment of disease. The history of nuclear medicine began with the discovery of radioactivity from uranium by the French physicist Antoine-Henri Becquerel in 1896, followed shortly thereafter by the discovery of radium and polonium by the renowned French chemists Marie and Pierre Curie. During the 1920s and 1930s radioactive phosphorus was administered to animals, and for the first time it was determined that a metabolic process could be studied in a living animal. The presence of phosphorus in the bones had been proven using radioactive material. Soon ³²P was employed for the first time to treat a patient with leukemia. Using radioactive iodine, thyroid physiology was studied in the late 1930s. Strontium-89, another compound that localizes in the bones and is currently used to treat pain in patients whose cancer has spread to their bones, was first evaluated in 1939.

A nuclide consists of any configuration of protons and neutrons. There are approximately 1,500 nuclides, most of which are unstable and spontaneously release energy or subatomic particles in an attempt to reach a more stable state. This nuclear instability is the basis for the process of radioactive decay , and unstable nuclides are termed radionuclides. During the 1940s and 1950s nuclear reactors, accelerators, and cyclotrons began to be widely used for medical radionuclide production. Reactor-produced radionuclides are generally electron-rich and therefore decay by β ⁻-emission. The main application of β ⁻-emitters is for cancer therapy, although some reactor-produced radionuclides are used for nuclear medicine imaging. Cyclotron-produced radionuclides are generally prepared by bombarding a stable target (either a solid, liquid, or gas) with protons and are therefore proton-rich, decaying by β ⁺-emission. These radionuclides have applications for diagnostic imaging by positron-emission tomography (PET). One of the most convenient methods for producing a radionuclide is by a generator. Certain parent–daughter systems involve a long-lived parent radionuclide that decays to a short-lived daughter. Since the parent and daughter nuclides are not isotopes of the same element, chemical separation is possible. The long-lived parent produces a continuous supply of the relatively short-lived daughter radionuclide and is therefore called a generator.

Currently, the majority of radiopharmaceuticals are used for diagnostic purposes. These involve the determination of a particular tissue's function, shape, or position from an image of the radioactivity distribution within that tissue or at a specific location within the body. The radiopharmaceutical localizes within certain tissues due to its biological or physiological characteristics. The diagnosis of disease states involves two imaging modalities: Gamma (γ ) scintigraphy and PET. In the 1950s γ scintigraphy was developed by Hal O. Anger, an electrical engineer at Lawrence Berkeley Laboratory. It requires a radiopharmaceutical containing a radionuclide that emits γ radiation and a γ camera or single photon emission computed tomography (SPECT) camera capable of imaging the patient injected with the γ -emitting radiopharmaceutical. The energy of the γ -photons is of great importance, since most cameras are designed for particular windows of energy, generally in the range of 100 to 250 kilo-electron volts (keV). The most widely used radionuclide for imaging by γ scintigraphy is ^99mTc (T _½ = 6 hours), which is produced from the decay of ⁹⁹Mo (T _½ = 66 hours). In 1959 the Brookhaven National Laboratory (BNL) developed the ⁹⁹Mo/^99mTc generator, and in 1964 the first ^99mTc radiotracers were developed at the University of Chicago. The low cost and convenience of the ⁹⁹Mo/^99mTc generator, as well as the ideal photon energy of ^99mTc (140 keV), are the key reasons for its widespread use. A wide variety of ^99mTc radiopharmaceuticals have been developed during the last forty years, most of them coordination complexes. Many of these are currently used every day in hospitals throughout the United States to aid in the diagnosis of heart disease, cancer, and an assortment of other medical conditions.

PET was developed during the early 1970s by Michel Ter-Pogossian and his team of researchers at Washington University. It requires a radio-pharmaceutical labeled with a positron-emitting radionuclide (β ⁺) and a PET camera for imaging the patient. Positron-decay results in the emission of two 511 keV photons 180° apart. PET scanners contain a circular array of detectors with coincidence circuits designed to specifically detect the 511 keV photons emitted in opposite directions. The positron-emitting radionuclides most frequently used for PET imaging are ¹⁵O (T _½ = 2 minutes), ¹³N (T _½ = 10 minutes), ¹¹C (T _½ = 20 minutes), and ¹⁸F (T _½ = 110 minutes). Of these, ¹⁸F is most widely used for producing PET radiopharmaceuticals. The most frequently used ¹⁸F-labeled radiopharmaceutical is 2-deoxy-2 [¹⁸F]fluoro-D-glucose (FDG). This agent was approved by the Food and Drug Administration (FDA) in the United States in 1999 and is now routinely used to image various types of cancer as well as heart disease.

The use of radiopharmaceuticals for therapeutic applications (α - or β ⁻-emitters) is increasing. The first FDA-approved radiopharmaceutical in the United States was, in fact, for therapeutic use. Sodium [¹³¹I] iodide was approved in 1951 for treating thyroid patients. There are currently FDA-approved radiopharmaceuticals for alleviating pain in patients whose cancer has metastasized to their bones. These include sodium ³²P-phosphate, ⁸⁹Sr-chloride, and ¹⁵³Sm-EDTMP (where EDTMP stands for ethylenediaminetetramethylphosphate). In February 2002 the first radiolabeled monoclonal antibody was approved by the FDA for the radioimmunotherapy treatment of cancer. Yttrium-90-labeled anti-CD20 monoclonal antibody is used to treat patients with non-Hodgkin's lymphoma.

Many branches of chemistry are involved in nuclear medicine. Nuclear chemistry has developed accelerators and reactors for radionuclide production. Inorganic chemistry has provided the expertise for the development of metal -based radiopharmaceuticals, in particular, ^99mTc radiopharmaceuticals, whereas organic chemistry has provided the knowledge base for the development of PET radiopharmaceuticals labeled with ¹⁸F, ¹³N, ¹¹C, and ¹⁵O. Biochemistry is involved in understanding the biological behavior of radiopharmaceuticals, while medical doctors and pharmacists are involved in clinical studies. Nuclear medicine, which benefits the lives of millions of people every day, is truly a multidisciplinary effort, one in which chemistry plays a significant role.

see also Becquerel, Antoine-Henri; Curie, Marie Sklodowska; Nuclear Chemistry; Nuclear Fission; Radiation Exposure; Radioactivity.

Carolyn J. Anderson

Bibliography

McCarthy, T. J.; Schwarz, S. W.; and Welch, M. J. (1994). "Nuclear Medicine and Positron Emission Tomography: An Overview." Journal of Chemical Education 71: 830–836.

Schwarz, S. W.; Anderson, C. J.; and Downer, J. B. (1997). "Radiochemistry and Radiopharmacology." In Nuclear Medicine Technology and Techniques, 4th edition, ed. D. R. Bernier, P. Christian, and J. K. Langan. St. Louis, MO: Mosby Year Book. utes),

Internet Resources

"A Brief History of Nuclear Medicine." UNM, Ltd. Available from <http://www.nucmednet.com/history.htm>.

"The History of Nuclear Medicine." Society of Nuclear Medicine. Available from <http://www.snm.org/nuclear/history.html>.