What is nuclear medicine?

Science and Profession

Nuclear medicine is the branch of medicine that uses radioactive substances in the diagnosis and treatment of diseases. A discussion of such technology requires an understanding of the nature of radioactivity and the tools employed by specialists in this medical field.

Radioactivity is the spontaneous emission of particles from the nucleus of an atom. Several kinds of emissions are possible. Gamma-ray emission is the type with which nuclear medicine imaging is concerned. The activity of radionuclides is measured in terms of the number of atoms disintegrating per unit time. The basic unit of measurement is the curie. Radiopharmaceuticals that are administered are in the microcurie or millicurie range of activity. Most radionuclides used in nuclear medicine are produced from accelerators, reactors, or generators. Accelerators are devices that accelerate charged particles (ions) to bombard a target. Cyclotron-produced radionuclides that are used frequently in nuclear medicine include gallium 67, thallium 201, and indium 111. The core of a nuclear reactor consists of material undergoing nuclear fission. Nuclides of interest in nuclear medicine that are formed from reactors include molybdenum 99, iodine 131, and xenon 133.

In generator systems, a “parent” isotope decays spontaneously to a “daughter” isotope in which the half-life of the parent is longer than that of the daughter. The parent is used to generate a continuous supply of the relatively short-lived daughter radionuclides and is therefore called a generator. The most commonly used generator system is molybdenum 99 (with a half-life of sixty-seven hours) and technetium 99m (with a half-life of six hours). The daughter, technetium 99m, is the most widely used radioisotope in nuclear medicine. It is obtained from the generator in a physiologic sodium chloride solution as the pertechnetate ion. It can be used alone to image the thyroid, salivary glands, or gastric mucosa, or it can be labeled to a wide variety of complexes that are picked up physiologically by various organ systems.

The scintillation camera, or Anger camera (named for its inventor, Hal O. Anger), is the most commonly used static imaging device in nuclear medicine. The scintillation camera produces a picture on a cathode-ray tube of the distribution of an administered radionuclide within the target organ of a patient. It uses the gamma rays emitted by the nuclide and a collimator to create the image as a series of light flashes on a disk-shaped sodium iodide crystal. The system determines the location of each scintillation and then produces a finely focused dot of light on the face of the cathode-ray tube in a corresponding position. The complete picture is then produced on photographic film. The camera normally contains two parts, the head and the computer console. The head serves as the gamma-ray detector. It absorbs incoming gamma rays and generates electrical signals that correspond to the positions where the absorptions took place. These signals are sent to a computer to be processed and to produce a picture that can be displayed on film or stored on disk for video display.

The collimator normally consists of a large piece of lead with many small holes in it. There are many types of collimators. The most commonly used are parallel-hole types. The holes are of equal, constant cross section, and their axes form a set of closely spaced, vertical, parallel lines. The materials between the holes are called septa.

Putting this all together, the radioisotope, once injected or ingested, travels to the target organ. Gamma rays from the target organ are emitted in all directions. The collimator allows only those gamma rays traveling in a direction essentially parallel to the axis of its holes to pass through to the crystal. The crystal is made of sodium iodide, with a small amount of thallium impurity. The thallium is transparent and emits light photons whenever it absorbs a gamma ray. This action by the collimator causes the light flashes in the crystal to form an image of the nuclide distribution located below it. This image will preserve gray-scale information, since the number of gamma rays received by any given region of the crystal will be directly proportional to the amount of nuclide located directly below that region.

Single photon emission computed tomography (SPECT) is a tomographic imaging technique employing scintillation cameras to display the information at a given depth in sharp focus, while blurring information above and below that depth. There are two distinct methods of SPECT, each based on the type of images produced. The first, longitudinal section tomography, provides images of planes parallel to the long axis of the body. The second method, transverse section tomography, is perpendicular to the long axis of the body. Transverse section tomography with a rotating gamma camera has received wide clinical acceptance, partly because of the information that it provides and its multiple-use capability, since these systems can perform routine planar imaging as well as SPECT imaging. In this system, the gamma camera is a device mounted to a gantry and capable of rotating 360 degrees around the patient. These systems must be interfaced with a computer. The orbit around the patient is circular, and from 32 to 180 equiangular images are acquired over a 360-degree arc. Image acquisition is by computer. The images are stored digitally, and image reconstruction is achieved by filtering each projection, with geometric correction for photon attenuation. Noise reduction is generally accomplished by the application of filters. The efficiency of rotating systems can be improved by incorporating additional detectors (most often two or three), which rotate around the patient. Virtually any organ in the body for which an appropriate radiopharmaceutical exists can be studied with SPECT techniques.

No overview of nuclear medicine would be complete without a brief description of positron emission tomography (PET) scanning. Positron-emitting radionuclides, such as carbon 11, nitrogen 13, oxygen 15, and fluorine 8 (a bioisosteric substitution for hydrogen), are isotopes of elements that occur naturally in organic compounds. These tracers enter into the biochemical processes in the body so that blood flow; oxygen, glucose, and free fatty acid metabolism; amino acid transport; pH; and neuroreceptor densities can be measured. A positron is an antimatter electron. This positron-emitting radiopharmaceutical is distributed in a patient’s system. As a positron is emitted, it travels several millimeters in tissue until it meets a free electron and annihilation occurs. Two gamma rays appear and are emitted 180 degrees apart from each other. A scintillation camera could be used to detect these gamma rays, but a collimator is not needed. Instead, the patient is surrounded by a ring of detectors. By electronically coupling opposing detectors to identify the pair of gamma rays simultaneously, the location where the annihilation event must have occurred (the coincidence) can be determined. The raw PET scan consists of a number of coincidence lines. Reconstruction could simply be the drawing of these lines as they would cross and superimpose wherever there is activity in the patient. In practice, the data set is reorganized into projections.

Diagnostic and Treatment Techniques

Nuclear medicine is widely used in the diagnosis and prognosis of coronary artery disease, especially in conjunction with either physical stress testing (treadmill or bicycle exercise) or pharmacological stress testing. The patient is instructed to exercise on the treadmill until his or her heart rate has significantly increased. At peak exercise, a radioisotope, usually thallium 201 or technetium 99m, is injected into a vein. Stress images are obtained. Because the injected tracer corresponds to the blood flow through the arteries that supply oxygen to the heart muscle, those vessels that have a blockage exhibit decreased flow, or decreased tracer delivered to that area of the heart. Rest images are also obtained. Rest and stress images are compared, and differences in the intensity of the tracer, analyzed by a computer, help to identify blocked arteries and the extent of the blockage. This technique is also used in follow-up of patients who have undergone bypass surgery or angioplasty to determine if blockage has recurred.

Nuclear cardiology is also used to measure the ejection fraction (the amount of blood ejected by the left ventricle to all parts of the body) and motion of the heart. Patients with cardiomyopathy, coronary artery disease, or congenital heart disease often have decreased function of the heart. Certain medications used in cancer therapy can also damage the heart muscle. These patients are followed closely to determine if they are developing toxicity from their drug therapy. In these studies, commonly called MUGA scans, a small portion of the patient’s blood is extracted. A radioactive tracer is tagged to this blood, which is then reinjected. The gamma camera takes motion pictures of the beating heart and, through the aid of computers, calculates the ejection fraction.

Nuclear medicine can be very helpful in locating primary or metastatic tumors throughout the body, and it is unique in its ability to assess the viability of a known lesion and its response to radiation or chemotherapy. Breast cancer, lymphomas (especially low-grade), differentiated thyroid cancer, and most sarcomas (both bone and soft tissue) are tumors that will metabolize the appropriate injected radiopharmaceutical. The resulting images will show increased localization in an active tumor but none in those masses that have been destroyed by treatment.

By injecting a radioisotope that has been tagged by bone-seeking agents, doctors can view images of an entire skeleton. Multiple fractures, metastatic disease, osteomyelitis, osteoporosis, and Paget's disease are but a few of the diseases that can be identified quickly and with minimal exposure of the patient to radiation.

Functional as well as anatomical information can be obtained by using nuclear medicine techniques to image the genitourinary tract, especially the kidneys. A perfusion study may be performed as the first phase of structural imaging. This study is done primarily to evaluate the vascularity (amount of blood vessels) of renal (kidney) masses. Cystic lesions and abscesses are usually avascular (having few or no blood vessels), and tumors are usually moderately or highly vascular. Uncommonly occurring arteriovenous (A-V) malformations show high vascularity. An evaluation of blood flow may also be important in patients who have received a kidney transplant. Anatomical renal imaging is performed to evaluate the position, size, and shape of the kidneys. Renal function studies have proven to be very sensitive in the diagnosis of both bilateral and unilateral kidney disease. By following specific tracers through the kidneys, doctors are able to evaluate the filtration by the glomeruli (capillary tufts) and the function of the tubules. Radionuclide cystography (imaging of the bladder), although not performed routinely, is extremely useful in diagnosing vesicoureteral reflux (urine reflux from the bladder back to the ureters), a relatively common problem in children.

Radionuclide imaging plays a significant role in the diagnosis of gastrointestinal disorders. Swallowing function, esophageal transit, gastroesophageal reflux, gastric emptying, gallbladder function, pulmonary aspiration of liver disease, and gastrointestinal bleeding can all be evaluated with nuclear medicine. The application of radioactive materials in the endocrine system provides historical benchmarks in the field of nuclear medicine with the use of radioiodine to assess the dynamic function of the thyroid gland. Radioiodine uptake testing is important and useful in the diagnosis of thyroid disease, specifically hyperthyroidism and hypothyroidism, thyroiditis, and goiters. Thyroid imaging is employed for the detection and functional evaluation of solitary or multiple thyroid nodules and the evaluation of aberrant thyroid tissue, metastases of thyroid cancer, and other tumors containing thyroid tissue.

The therapeutic value of nuclear medicine is best demonstrated in its role in the treatment of Graves disease, toxic adenoma, toxic multinodular goiter, and metastatic thyroid carcinoma. The purpose of the therapeutic application of radioiodine to hyperthyroidism (an overactive thyroid) is to control the disease and return the patient to a normal state. The accumulation and retention of radioiodine, with the subsequent radiation effects upon the thyroid cells, underlie the basic principle behind radionuclide therapy. The treatment of thyroid carcinoma with radioiodine is directed toward the control of metastatic foci and palliation of patients with thyroid carcinoma. Not all thyroid tumors localize radioiodine; therefore, care must be taken for proper patient selection by assuring a tumor’s response to iodine.

Monoclonal antibody imaging has become important not only diagnostically but also therapeutically. Antibodies with perfect specificity for antigens of interest—in this case, malignancies—are produced. These antibodies are labeled with a large dose of radioactivity and injected into the patient. This “magic bullet” is then directed only to the antigen-producing areas. As in thyroid treatment, the radiation effect destroys only those cells to which the radioactivity is attached, leaving the noncancerous cells undamaged. Although this treatment is primarily a research protocol, the future role of radioactive monoclonal antibodies in the treatment of malignant disorders could be significant.

Clinical applications of PET scanning have focused on three areas: cardiology, oncology, and neurology/psychiatry. The principal clinical utility of PET in cardiology lies primarily in accurately differentiating infarcted, scarred tissue from myocardium, which is viable but not contracting because of a reduced blood supply. PET offers a noninvasive procedure to distinguish tissue viability, which allows more accurate patient selection for surgery and angioplasty than conventional approaches. In cancer cases, PET can determine cellular viability and the growth of tumor tissue. It can directly measure the effectiveness of a given radiation or chemotherapy regimen on the metabolic process within the tumor. PET can differentiate tumor regrowth from radiation necrosis.

Because of the unique ability of PET scanning to assess metabolic function, it can aid in the diagnosis of dementia and other psychoses as well as offer possible effective treatment of these disorders. PET is also helpful in detecting the origin of seizures in patients with complex epilepsy and can be used to locate the lesion prior to surgical intervention. Strokes are one of the most common causes of death in the United States. PET can determine the viability of brain tissue after a stroke, permitting the clinician to select the most effective (and least invasive and expensive) form of treatment.

Nuclear imaging techniques are quite safe. Allergic reactions to isotopes are essentially nonexistent. In fact, the few that have been reported can be traced back to a contaminant in the injected dose. The radiation burden is far less than that of fluoroscopic radiographic examination and is equal to that of one chest x-ray, regardless of the picture produced.

Perspective and Prospects

Natural radioactivity was discovered in the late nineteenth century. The first medical success with a radioisotope was Robert Abbe’s treatment of an exophthalmic goiter with radon in 1904. In 1934, the Joliot-Curies produced artificial radioisotopes, specifically phosphorus 32. In 1938, Glenn T. Seaborg synthesized iodine 131. Phosphorus 32 was used to treat chronic leukemia and iodine 131 to treat thyroid cancer. Both treatments fell victim to radiation hysteria fueled by the aftermath of World War II. For a decade, nuclear medicine was equated with the “atomic cocktail” and was used only sporadically as a therapeutic modality. In 1949, the first gamma camera was introduced by Benjamin Cassen. It was called a tap scanner because as it measured radioactivity, it would tap ink on a piece of paper. The intensity of the ink mark was directly proportional to the radioactivity that was being scanned. The first nuclear medicine image was that of a thyroid gland.

Although discovered in the late 1930s, the imaging properties of the short-lived technetium 99m were not understood until the early 1960s. Its six-hour half-life and its chemical properties were ideally suited to imaging with the scintillation camera newly introduced in 1965. From that time on, nuclear medicine grew in its role as a diagnostic tool, with technetium agents becoming the primary radiopharmaceuticals employed in the detection of disease.

With the addition of computers and array processors to the technology, tomographic imaging became increasingly useful in the localization and quantification of disease states. Improved body attenuation correction and computerized three-dimensional imaging enable physicians to quantify the size and extent of abnormalities quite accurately. When one examines the relative role and costs of transmission computed tomography (CT) scanning versus SPECT, a number of factors must be kept in mind. On the side of advantage of SPECT are the low costs compared to CT scanning. Additionally, no contrast is required in the SPECT study, which lessens the chance of adverse patient reaction. CT scanning is still primarily an anatomic diagnostic tool, while SPECT, by employing physiological radiopharmaceuticals, demonstrates the functional features of organs. By repeated imaging during the course of treatment, minute changes in the physiologic biochemical process can be detected and appropriately addressed.

Because of the physiologic nature of nuclear medicine, the development of radiopharmaceuticals to detect other disease states is essential for further growth in this field. It is interesting that much activity in this area is now centered on the treatment of diseases, primarily malignant ones. As PET scanning becomes more frequently used, new positron radiopharmaceuticals will be introduced. Theoretically, all biochemical reactions in the body can be imaged, if the proper radiopharmaceutical is produced.

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