NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.
Institute of Medicine (US) Committee for Review and Evaluation of the Medical Use Program of the Nuclear Regulatory Commission; Gottfried KLD, Penn G, editors. Radiation In Medicine: A Need For Regulatory Reform. Washington (DC): National Academies Press (US); 1996.
Institute of Medicine (US) Committee for Review and Evaluation of the Medical Use Program of the Nuclear Regulatory Commission; Gottfried KLD, Penn G, editors.
Washington (DC): National Academies Press (US); 1996.This chapter provides an overview of the wide array of clinical applications of ionizing radiation. As is customary, applications are grouped here into diagnostic and therapeutic uses. These two categories are further divided by whether the ionizing radiation is administered through external or internal sources.
Also of importance for understanding this area of medicine are the many different medical conditions for which these clinical applications are critical and the levels of exposure to radiation involved in each procedure. This last information is important because the known or perceived risks from these clinical applications are related directly to exposure levels. It is against these risks that government regulation is primarily aimed. Thus, this chapter also discusses the forms that government control takes over the various sources and uses of ionizing radiation. As will become apparent to the reader, the divisions of regulatory authority do not clearly correspond to the risks associated with the sources and applications.
As an aid to the reader, Table 2.1 provides a chart of radiation sources and their applications. In addition, a preliminary section introduces some terminology about how levels of radiation are customarily denoted. The following two main sections of the chapter discuss in turn the diagnostic and the therapeutic applications of ionizing radiation. These sections are followed by the chapter's conclusion.
Radiation in Medicine.
Initial systematic studies of patient exposure, beginning in the 1970s, used an index called "entrance skin exposure" in units of milliroentgen (mR). Since that time, the metrics used in science and medicine have changed to internationally accepted units, and the relevant index in radiology is now ''entrance skin air kerma" (ESK) in units of milligray (mGy). An entrance skin exposure of 100 mR is equivalent to an ESK of 0.869 mGy; both measures quantify the intensity of x-rays in air at the patient's skin.
To calculate a patient's radiation dose for a specific organ for a given ESK, radiologists must consider both the attenuation and the scattering of the x-ray within the patient. To help in this process, the Food and Drug Administration (FDA) of the Department of Health and Human Services and others have published tables and computer codes that give the dose to various organs per unit ESK for many different radiographic procedures. To estimate patient risk or to compare a nonuniform exposure to whole body exposure, the International Commission on Radiological Protection recommends that individual organ doses be converted to "effective dose equivalent" (EDE) in units of millisievert (mSv). 1 EDE is the dose that, if delivered uniformly, would have the same biological effect as the actual (nonuniform) dose. It is calculated as the product of individual organ dose and an "organ weighting factor" given by the International Commission on Radiological Protection.
Collective dose equivalent is the product of EDE and the number of persons receiving a radiation dose; it is expressed in units of person-sievert (person-Sv). Collective dose equivalent for diagnostic medical x-rays, for example, can be estimated as the product of the EDE per procedure and the total number of procedures.
Collective dose equivalent is of interest in terms of broad population exposure to radiation overall and to radiation from various medical uses. If medical uses produced a very high exposure compared to the exposure levels encountered in ordinary daily activities, policymakers and others might have reason to direct relatively more attention to the regulation of medical uses of ionizing radiation. Conversely, if it is the case that common daily activities expose the general population to radiation levels significantly far in excess of those from medical applications, policymakers might have less reason or interest in such regulation.
The discussions that follow present information on radiation exposure from various procedures in some depth, with the aim of providing the reader with a sense of the inherent risk (or lack of it) of various techniques that use ionizing radiation. These interventions are by no means the only source of exposure to radiation in this country, however. Normal background radiation from all natural sources (including radon) in the United States exposes each member of the population to an average EDE of about 3 mSv per year.
The diagnostic uses of ionizing radiation are classified below under two basic headings: radiology and nuclear medicine. In radiology, the radiation administered is external to the patient; in nuclear medicine, it is internal. The discussion of each of these two classes of applications addresses types of procedures, utilization, radiation doses, and radiation regulation and control.
In the 100 years since the discovery of x-rays, diagnostic radiology has grown from a scientific curiosity to a pervasive and essential part of modern health care. Radiology originated with the use of ionizing radiation to diagnose human disease. The development of nonionizing technologies, such as ultrasound and magnetic resonance imaging (MRI), has led to the more generic term "medical imaging." Indeed, the fastest growing areas of radiology are these two nonionizing modalities. Nevertheless, x-ray imaging continues to comprise 80 to 90 percent of all imaging procedures. It is performed using three different imaging techniques: radiographic imaging, fluoroscopic imaging, and computed tomography (CT).
The physical principle underlying x-ray imaging is the partial transmission of x-rays through the body. An external source produces x-rays, and this radiation interacts with tissues in the patient's body either through absorption or scattering. The degree of interaction depends on various factors (such as the energy of the x-rays and the density of tissues traversed). The three main imaging techniques rely on different mechanisms for detecting, viewing, or recording the x-rays emerging from the patient's body. 2 In all cases, however, the essential interaction of x-rays with tissue produces an unwanted, but unavoidable, consequence, namely the deposit of some radiation dose in the patient.
The vast majority of x-ray procedures are performed by radiographic imaging. These radiographic imaging procedures are in turn typically divided into what are considered "conventional" examinations, on the one hand, and "contrast studies," on the other.
Conventional examinations. Most notable among the conventional examinations is chest radiography, the most common of all radiographic imaging procedures. It is widely available (even at bedside, using portable x-ray machines), low in cost, and conveniently repeated to assess clinical changes. It is a primary tool in the diagnosis of diseases of the lungs (particularly infectious disease and cancer); it provides information on midline anatomical structures and the cardiovascular system (e.g., for diagnosing congestive heart failure); and it is useful for monitoring the status of critically ill patients. At times, chest radiography has been used ineffectively and inappropriately (e.g., for certain screening or administratively required examinations or for routine hospital admission). To reduce unnecessary utilization, professional organizations have established standards for its performance. Chest radiography may undergo technological modification in the future, such as the use of digital image receptors, but it will likely remain the most prevalent imaging examination.
Other conventional examinations include those of the extremities, spine, skull, abdomen, pelvis, and breast. Radiographic views of the extremities are the most efficient way to diagnose broken bones and injured joints, but radiographic imaging is now less common than before for several other parts of the body. For example, CT and MRI examinations have largely replaced radiographic imaging of the spine and skull for central nervous system evaluation, and body CT and ultrasound have somewhat reduced the use of conventional radiographic examinations of the abdomen and pelvis.
Mammography is an example of a radiographic imaging procedure that now plays a critical role in the diagnosis of a major health problem in this nation. It has undergone dramatic improvement in image quality and reduction in patient dose, and the development of units dedicated exclusively to mammography has optimized the total radiographic system (from x-ray tube to film-screen cassette) for breast imaging. The consequences of these technological advances are significant. For example, in women older than 50 years of age, screening mammography is the best method for early detection of breast cancer. As part of a comprehensive program of screening, follow-up, and treatment, mammography can be expected to yield a 30 to 50 percent reduction in breast cancer mortality (Feig, 1995; Tabar et al., 1995).
Contrast studies. Contrast studies are a wide range of radiographic imaging studies in which the patient is administered an agent to improve contrast in the x-ray image. For example, patients ingest or are injected with compounds containing barium (oral) or iodine (oral and intravenous) or with low-density agents such as air. Contrast agents have been used in imaging of the alimentary tract (upper gastrointestinal (UGI) series and barium enema), the urinary tract (intravenous pyelogram), the gall bladder (oral cholecystogram), and the spinal cord (myelogram).
The frequency of contrast studies decreased from 1970 to 1980, as competing techniques (e.g., endoscopy and colonscopy for alimentary tract evaluation, ultrasound and CT for body evaluation, and CT for central nervous system evaluation) became available. The advent of MRI in the 1980s accelerated this decrease. In general, the trend away from contrast studies can be attributed to various technological, medical, and economic factors, such as improved diagnostic accuracy, reduced risk of medical complications, and the changing content of various physician specialties. For instance, myelography is much less frequently performed because MRI yields superior images and requires no needle puncture of the spinal canal. As another example, although the double-contrast UGI series yields diagnostic results and clinical outcomes nearly identical to those of endoscopy at one-third the cost, endoscopy has largely supplanted the UGI series in many institutions, in part owing to the establishment of gastroenterology as a procedure-oriented subspecialty.
Another form of contrast study is the "special" 3 or intravascular procedure. Here, a catheter is introduced into an artery or vein and directed to an area of interest. Once in position, an iodinated contrast agent is injected into the catheter while many images (tens to hundreds) are rapidly obtained. In many instances, radiologists perform a subtraction study, in which an image with contrast agent present is subtracted from an identical image without contrast to yield an image of just the vascular anatomy.
There are several variations of these special procedures. Cerebral angiography is performed to evaluate conditions such as vascular obstructive disease, aneurysm, arteriovenous malformation, and brain tumor. Visceral and peripheral angiography studies are performed to evaluate obstructions and aneurysms in the vascular system. Cardiovascular procedures are done to measure heart functional capacity and to assess coronary artery obstruction.
The most recent detailed data about the rates of use of radiological diagnostic procedures date to work by the National Council of Radiation Protection (NCRP) for 1980 (NCRP, 1989), as presented in Table 2.2. As these data indicate, the chest x-ray examination is by far the most common procedure (accounting for over one-third of all procedures tabulated); it is followed by examinations of the extremities (about one-quarter) and of the spine (thoracic, lumbar and full, adding to about one-tenth).
Relative Frequency and Absolute Utilization Rate of Radiological Procedures in 1980.
Although broad-based data are sparse at best, the total numbers of procedures and rates per 1,000 population have certainly increased in the intervening years. In addition, the relative distribution among types of procedures has undoubtedly changed in response to new imaging modalities and shifts in the settings in which radiological examinations are done.
In 1980, approximately 80 to 85 percent of all radiological procedures were estimated to have been performed in hospitals (for both inpatients and outpatients), and the remaining 15 to 20 percent were done in physician offices or outpatient imaging centers. By 1990, approximately 25 to 35 percent of all imaging procedures were estimated to occur outside of hospitals (Sunshine et al., 1991). The trend towards nonhospital-based imaging has accelerated since 1990, as health care providers have reacted to market and reimbursement forces by moving imaging procedures outside the hospital setting.
No studies have updated the distribution of procedures at the level of detail reflected in Table 2.2 Some more recent information on specific diagnostic modalities is available, however. The frequency of CT use has greatly increased, from about 2 percent of radiological procedures (excluding ultrasound and MRI) in 1980 to about 7 percent in 1990. The rates of some procedures, such as plain films of the skull or lumbar spine and contrast studies of the GI tract, have probably decreased.
Over the years, several agencies, associations, and individuals have developed data on the total volume of imaging procedures. These include the FDA, the NCRP, and the American College of Radiology (ACR) (see Johnson and Abernathy, 1983; NCRP, 1989; Sunshine et al., 1991; Mettler et al., 1993). Since the compilation of the information presented in Table 2.2, less detailed surveys (which have not broken down rates for specific imaging procedures) have been published. Table 2.3 gives information for hospital-based procedures for 1970, 1980, and 1990. In this 20-year period, the total number of imaging procedures in hospitals rose by two and a half times, from just under 82 million procedures to more than 206 million, with a steep growth rate in the use of CT, ultrasound, and MRI.
Total Number (in thousands) of Imaging Procedures in U.S. Hospitals, 1970–1990.
The upward trend in the overall use of diagnostic radiology procedures, including both those provided in hospitals and those provided in nonhospital settings such as physician offices and freestanding centers, is slightly smaller in percentage terms but dramatic nonetheless. Data in Table 2.4 indicate that the total number of procedures more than doubled, from 136 million to 294 million, between 1970 and 1990, resulting in rates per 1,000 persons of 670 and 1,180, respectively. While the total utilization rate of all imaging procedures per 1,000 population grew 48 percent from 1980 to 1990, rates of procedures that expose patients to ionizing radiation rose only about 28 percent. The 1990 figures cited here are based on fairly crude estimates, but they are the best available at this time. No work has been published in recent years to assess the impact of managed care or other cost-containment strategies on the use of diagnostic radiology services.
Estimated Total Number of All Medical Imaging Procedures, 1970–1990.
It should be emphasized that the charge to the committee was to assess the Nuclear Regulatory Commission's (NRC's) Medical Use Program and problems related to misadministrations. Consequently, the committee did not examine the overuse of radiation in medicine, which is probably best addressed by professional training and patient advocacy.
Radiation dose and the immediate or short-term adverse consequences of diagnostic radiology procedures are of concern to the health care professions, the public, and regulators. Radiation dose depends on numerous factors, including the size of the patient, the radiation sensitivity of the image receptor, the energy of the x-ray beam, the radiation exposure rate, and the total time the x-ray tube is energized. Because exposure of both individual patients and populations is of concern, measurements are taken for both person-specific exposure (e.g., ESK and EDE, see above) and collective dose equivalent.
Patient-specific radiation dose. Table 2.5 provides, for several common imaging procedures, comparative information related to some of these factors: the average ESK per image, the average EDE per procedure (which can include multiple images), and the level of EDE from the procedure, expressed as a percentage of background radiation.
Typical Entrance Skin Air Kerma (ESK) per Procedure and Typical Effective Dose Equivalent (EDE) for Several Common Procedures.
Although extensive surveys have not been done since the early 1980s, experts believe that in the 1990s, the EDE of some of these diagnostic procedures may be lower than the figures given in Table 2.5. 4 Better technology (e.g., wider use of highly sensitive rare-earth phosphor intensifying screens) explains the reduction. For example, Rueter et al. (1992) report that surveys conducted in 1973, 1981, and 1987 showed, respectively, an average anterior/posterior lumbar spine ESK of 6.55, 5.57, and 3.65 mGy; the entrance exposure dropped by 35 percent from 1981 to 1987 and was almost half of the 1973 value. Values for chest radiography did not decrease as dramatically.
Unlike conventional fluoroscopic procedures such as the UGI or barium enema (with typical exposure times of less than 5 minutes), special and interventional procedures can involve long exposure times (20 minutes or more), prompting additional concern about radiation dose. Some experts are also wary of fluoroscopic equipment that is operated in a high radiation output mode in order to reduce noise and improve image quality for catheter placement (Cagnon et al., 1991). Several instances have been reported of high skin doses of several hundred rem resulting in acute effects such as radiation burns and hair loss. Professional societies, the FDA, and equipment manufacturers have taken steps to address these problems (ACR, 1992).
Collective dose. The NCRP developed an estimate of collective dose equivalent for x-ray procedures in 1980, the last year sufficient data were available for accurate calculation (Edwards, 1995). In that year, the total collective effective dose to the U.S. population (average EDE per procedure times total number of procedures) was 92,000 person-Sv, or about 0.40 mSv per person. This is not an especially high rate, compared to natural background radiation levels in this country of 3 mSv per person. It implies that x-ray diagnostic imaging adds about 13 percent to the radiation dose for the general population that comes solely from our daily environment.
These figures might be used to calculate the potential risk of death from radiation exposure. However, the NCRP noted that if this collective dose were used to estimate mortality risks, the resulting figure would overestimate actual risk. Risk coefficients (fatalities per person-Sv) assume a population at risk identical in age, sex, and other characteristics to the U.S. population as a whole. These assumptions are faulty, however, for several reasons. Older people, for instance, who are more likely to receive medical x-rays, are generally beyond child-bearing age. In addition, the latency period for certain cancers may be greater than the average life expectancy of these older age groups. When these factors are taken into account, in a "weighted" collective dose equivalent, the per-person figure (for 1980) decreases from 0.40 mSv to about 0.25 mSv, which is less than 10 percent more than the typical background levels of exposure for the U.S. population.
No precise collective dose estimates have been published for 1990. If one assumed that EDE per procedure and the relative frequencies of procedures performed did not change, then collective dose equivalent would track utilization directly. From 1980 to 1990, the total number of x-ray procedures rose about 40 percent while the population increased 10 percent. These figures yield crude estimates of an annual collective dose of 129,000 person-Sv and a per-person EDE of 0.52 mSv.
These last values are probably overestimates, however, for two reasons. The relative frequency of some x-ray procedures (such as those for the skull and alimentary tract) that deliver relatively higher doses has probably remained the same or decreased. Furthermore, higher speed image receptors are more prevalent. Studies using very high dose radiation, such as special and interventional procedures, have not been included in this estimate, but they may not have a great impact because of their relatively low utilization rates.
Control and regulation of diagnostic x-rays are divided among local, state, and federal agencies. Qualifications and training of physicians and equipment operators are usually regulated by state, rather than federal, law. State standards are far from uniform. Although x-ray equipment manufacture is controlled by federal statute, public and occupational exposures are regulated by state statute. Thus, states regulate the medical uses of x-rays, from simple chest x-rays to cerebral angiography.
An exception to the generally laissez-faire attitude of the federal government toward clinical diagnostic imaging is mammography. The Mammography Quality Standards Act, effective in 1994, sets forth very detailed federal statutes for the regulation of the approximately 11,000 mammography centers in the United States. Part 900 of Title 21 of the Code of Federal Regulations (CFR) sets criteria for physician residency training in mammography and for subsequent continuing medical education; minimum film interpretation work loads; and equipment performance, calibration, and quality assurance standards. The law also requires annual inspections of each facility to assure compliance. No similar federal programs exist for other areas of diagnostic imaging.
No law directly limits the total amount of radiation received by an individual patient in the course of a medical procedure. The decision to recommend a diagnostic or interventional procedure involves medical judgment concerning the radiation risks (and other risks, such as reaction to contrast agents), compared with the medical benefits as they apply to the unique circumstances of individual patients. An increased chance of cancer associated with even a high dose neurointerventional procedure is well justified if the alternative is failure to control intracranial bleeding. Conversely, the extremely low excess risk associated with a chest radiograph is unwarranted if there is no medical reason to perform the procedure. Although it is inappropriate (and probably impossible) to control patient exposure through legally imposed patient dose limits, control of professional standards, qualifications, and training does have a direct impact on patient dose.
Manufacture and installation of medical x-ray equipment are regulated by the FDA, through 21 CFR Part 1020. These regulations, which apply to radiographic, fluoroscopic, and CT equipment sold in the United States, set equipment performance standards for items such as tube housing leakage, beam filtration, beam collimation, accuracy and reproducibility of technique factors, and fluoroscopic exposure rates. Equipment installers supply certificates of compliance to the FDA for all newly installed equipment. These reports also are used by the states as a means of registering new equipment for state radiation control programs.
Medical x-ray safety of the public and occupationally exposed workers is controlled by the states. Dose limits and other regulations set by the NRC for medical use of byproduct material do not apply to x-ray sources. However, the Occupational Health and Safety Administration sets similar dose limits for workers not covered by NRC regulations. The Conference of Radiation Control Program Directors maintains a standing committee to produce a uniform set of suggested regulations. These Suggested State Regulations for Control of Radiation are used by state departments of radiological health as guidance for formulation of state law. Local governments at the county and city level sometimes impose additional regulations on occupational exposure and medical x-ray equipment.
Nuclear medicine is the medical and laboratory specialty that employs the nuclear properties of radioactive and stable nuclides to evaluate metabolic, physiologic, and pathologic conditions of the body. Relying on an ever-growing number of radiopharmaceuticals (pharmaceuticals marked with a radioactive agent so that they may be traced), nuclear medicine laboratories perform a host of diagnostic procedures, including studies of the thyroid, cardiac system, liver, kidney, lung, and gastrointestinal systems, as well as studies of mineral metabolism and the entire body.
Nuclear imaging. In nuclear imaging, clinicians either inject small amounts of radiopharmaceuticals into patients intravenously or have patients inhale or ingest the material. Depending on the metabolic pathways of the pharmaceutical in question and disease status of the patient to be studied, the radiopharmaceutical is distributed nonuniformly throughout the body. Gamma rays emitted from these locations escape the body and are imaged by means of a position-sensitive scintillation detector, commonly called a gamma camera.
The efficacy of such studies depends on the tracer principle and on the ability to detect many of the radioactive agents used without disturbing the anatomic system under study. The tracer principle is that very small amounts of materials with particular chemical and physical identities will follow natural physical and biochemical pathways and allow detection instruments to sense the radioactivity from outside the patient. Detectors range from probes that are aimed at a particular part of the patient to extremely sophisticated instruments that compute three-dimensional images of distributions of radioactivity in the patient.
Compared with other imaging technologies such as radiography and CT, discussed above, standard gamma cameras produce considerably less sharp images. This lower resolution of nuclear medicine images is not a major drawback, however, because the clinical utility of nuclear medicine imaging stems primarily from its ability to assess physiologic function rather than anatomy. That is, clinicians pay particular attention to detection and measurement of abnormal organ function rather than to altered organ structure.
Tracer compounds are usually labeled with technetium-99m (Tc-99m), a radionuclide that decays with a 6-hour half-life, but other agents are also used. Among the more common are thallium-201 (Tl-201), xenon-133 (Xe-133), iodine-123 (I-123), iodine-131 (I-131), and gallium-67 (Ga-67).
Used alone or in combination, these nuclides enable diagnosis of a multitude of conditions. These include coronary artery disease (a decrease in blood supply to the heart caused by the narrowing of the blood vessels), pulmonary embolism (a life-threatening blockage of lung blood flow), thyroid carcinoma, brain disorders, acute cholecystitis (an inflammation of the gall bladder), gastrointestinal bleeding, renal artery stenosis (a frequent cause of elevated blood pressure), bone cancer, and even acute fevers of unknown origin. This list is but a small sample. The diagnoses arrived at through nuclear medicine not only name the illness, but also allow physicians to make complicated decisions, such as when stop chemotherapy that is damaging heart muscle, how to plan surgery before removal of lung segments, when to treat a patient for Cushing's syndrome (hypercortisolism) as opposed to Conn's syndrome (hyperaldosteronism), and whether to ready a patient's family for the onset of Alzheimer's disease.
Current trends in clinical nuclear medicine include an emphasis on radioimmunodiagnosis, single photon emission computed tomography (SPECT), and positron emission tomography (PET). In radioimmunodiagnosis, newly developed monoclonal antibodies are used to detect a variety of cancers and to trace myocardial infarction. SPECT and PET are techniques that offer the special advantages of cross-sectional imaging, analogous to x-ray computed tomography. SPECT is already widely applied as a major improvement of nuclear imaging. PET has very special advantages for sensitivity and resolution as well as significant potential for the evolution of new, physiologically important tracers. For full implementation of the PET method, a high-energy accelerator (cyclotron) is required to produce short-lived nuclides that decay by positron emission. PET is now available in many major centers, but it has not yet diffused to community hospitals.
Radionuclides and radiopharmaceuticals. Radiopharmaceuticals used for nuclear medicine imaging are categorized by the radionuclide and the pharmaceutical to which it is bound. The physical characteristics of the radiopharmaceutical (which include photon energy, physical half-life, and particulate decay products) are determined by the radionuclide, whereas physiological properties (such as uptake site, metabolism, and biological half-life) are determined by the pharmaceutical.
Half-life is a particularly important issue for the exposure of patients (and others) to radiation, because as half-life decreases, a greater fraction of the total decay occurs during the image acquisition. For example, the ideal radionuclide for imaging with a gamma camera (a) decays with the emission of only gamma rays (to reduce patient dose), (b) has a low gamma ray energy (to escape from the patient, yet still be detected with high efficiency and high intrinsic resolution by the gamma camera), and (c) decays with a physical half-life on the order of minutes to hours. 5 Table 2.6 summarizes the half-life properties of radionuclides commonly used for nuclear medicine imaging. As seen there, the half-life ranges from 2 minutes (oxygen-15) to 8 days (iodine-131). Approximately 85 percent of nuclear medicine imaging studies are performed with pharmaceuticals labeled with Tc-99m, which has a half-life of 6 hours. The physical properties of this isotope closely approximate those of the ideal radionuclide.
Properties of Radionuclides Used in Common Nuclear Medicine Procedures.
The total numbers of nuclear medicine procedures are available for the past 20 years from various sources. Table 2.7 provides annual counts of several nuclear medicine procedures in various body systems for 1972, 1982, and 1993. As can be seen, in 1993, the total number of procedures exceeded 8 million. In the 20-year period, the number of bone imaging procedures increased dramatically, as did those on the cardiovascular system; conversely, brain imaging procedures dropped.
Number of Nuclear Medicine Procedures (in thousands) by Examination Type.
The annual procedure rate per 1,000 population was 16, 33, and 33 examinations in 1972, 1982, and 1993, respectively. After a period of rapid expansion in the 1970s, nuclear medicine utilization has grown only as fast as the population. The impact of CT and MRI accounts for the decrease in brain procedures as well as for the slower growth rate (compared with the 1970s) of a number of procedures related to other parts of the body.
Patient-specific radiation dose. Radiation dose from nuclear medicine procedures depends on the radiopharmaceutical, the administered activity, and individual patient metabolism. Because the radiopharmaceutical is taken up in a nonuniform manner, the organ dose varies dramatically. To aid in clinical applications, radiopharmaceutical manufacturers provide dosimetry estimates based on standardized adult and child metabolic and anatomic models. For each procedure, the activity for a typical dose is calculated for individual organs and for the whole body. In combination with organ weighting factors, EDEs can also be calculated. Table 2.8 shows administered activity, absorbed dose of the maximally exposed organ, EDE, and fraction of EDE relative to normal background for several common nuclear medicine procedures.
Dosage Levels for Several Nuclear Medicine Procedures.
With the exception of the I-131 sodium iodine thyroid scan, the EDE per procedure varies from one-tenth to several times the 3 mSv of natural background radiation. The I-131 sodium iodine gives an extremely high thyroid dose (almost 2,000 times background), because beta particles (electrons) emitted during radioactive decay are absorbed locally in thyroid tissue. Nuclear medicine procedures generally result in slightly higher patient exposure compared with diagnostic x-ray procedures. The reasons for this include the higher doses necessary for image clarity, the exposure time required for observing certain biological functions, and the fact that the radioactive material is not immediately flushed from the system, but continues to decay in the patient's body after the procedure is complete.
Collective dose. The NCRP has estimated collective dose to the U.S. population from diagnostic nuclear medicine procedures using the same approach discussed earlier for diagnostic radiology (average EDE per procedure times total number of procedures). For 1982, the NCRP produced an estimate of 32,100 person-Sv, with a per-person EDE of 0.14 mSv (Edwards, 1995).
The relevance of these figures is that, compared with medical x-rays, diagnostic nuclear medicine contributes a lower collective dose and a lower per-person dose. The reason is that the total number of nuclear medicine procedures is much lower than that of medical x-ray procedures. Age-weighted collective dose (which takes into account the older age of the patient population) was 13,500 person-Sv in 1982. Because nuclear medicine is not expanding faster than the population, collective dose for 1993 should scale to the U.S. population in that year. This would result in a collective dose of 35,400 person-Sv and a per-person dose still at 0.14 mSv.
Radiation regulation and control of medical nuclides and radiation safety in nuclear medicine are historically rooted in federal statutes. Many of the radionuclides used in nuclear medicine are produced using a nuclear reactor. Reactor development grew out of the World War II Manhattan Project, and all reactor related issues were regulated by the federal government through the Atomic Energy Commission until 1974. When the Atomic Energy Commission was split in that year into the NRC and the Energy Research and Development Agency (now the Department of Energy), regulation of the medical use of reactor-produced radionuclides was given to the NRC.
The NRC does not regulate all aspects of medical radionuclides, however. Accelerator-produced radionuclides, such as T1-201, Ga-67, and indium-111 (In-111), are controlled by state regulation. Table 2.9 lists byproduct radionuclides that fall within NRC regulatory authority, and Table 2.10 lists accelerator-produced radionuclides that are regulated, if at all, by the states.
Selected Reactor-Produced Radionuclides and Their Biomedical Applications.
Selected Accelerator-Produced Radionuclides and Their Biomedical Applications.
As noted in Chapter 3, regulation in this area is widely dispersed across agencies in the federal government. For example, shipping and receiving of radionuclides are regulated by the Department of Transportation. Disposal of non-reactor-produced radionuclides is regulated by the Environmental Protection Agency.
A further complication is that states may agree to regulate reactor-produced nuclides on their own. Such Agreement States (see Chapter 3) must have state regulations that meet or exceed federal regulations. Twenty-nine states, including most of the heavily populated states, are Agreement States. Hence most nuclear medicine procedures are performed in Agreement States, under the direction of state regulations.
Because state regulations cannot be weaker than federal regulations, the regulation of nuclear medicine is essentially determined by 10 CFR Parts 20 and 35. Part 20 sets forth general radiation protection standards and regulations; Part 35 covers medical uses of radionuclides. Regulation is achieved through licensing of institutions and "authorized users."
To receive, possess, or administer medical radionuclides, an institution must be issued a license that commits the institution to observe NRC rules and regulations, as set forth in the CFR and expanded on in "Regulatory Guides." Typically, a hospital must have a radiation safety committee, a radiation safety officer, a high-level administrative commitment to the provisions of the radiation safety program, written policies and procedures for radiation safety and isotope utilization that are substantially identical to NRC model guidelines, and sufficient resources and manpower to carry out the program.
To receive and administer radionuclides, a physician must be named on the license as an authorized user. This requires either specialty board certification or completion of several hundred hours of prescribed course work in addition to a medical degree. The regulations do not prohibit a physician who is not an authorized user from interpreting nuclear medicine images.
In response to concerns about "misadministrations," which are defined as incidents in which the wrong nuclide or a wrong amount of the nuclide was administered to a patient, the NRC now requires hospitals to institute a "quality management" (QM) program (see Chapter 3). Although this program applies primarily to therapeutic radionuclides, any diagnostic study involving more that 30 microcuries of I-131 sodium iodine (see Table 2.10) must follow special policies and procedures. For instance, there must be a "written directive" signed by an authorized user prior to administration, the activity must be independently checked, and the patient must be identified by two independent means. Records of nuclide administrations must be reviewed quarterly and the entire program annually. Whether such programs will have an impact on the misadministration rate remains to be seen.
Ionizing radiation applied for therapeutic (as contrasted with diagnostic) purposes is also typically classified into categories based on whether the source of the radiation is external or internal to the patient. Respectively, these areas are called radiation oncology and teletherapy (external sources), brachytherapy (internal), and therapeutic nuclear medicine (internal). Each of these areas is discussed below.
Radiation oncology is the specialty of medicine that deals with treating cancer patients with ionizing radiation. It employs teletherapy, which is radiation therapy delivered by an external beam of radiation, as described below. Radiation therapy is also used to treat noncancerous conditions on a selective basis.
At the present time, at least 50 to 60 percent of all cancer patients receive radiation therapy sometime during the course of their illness. The intent of this treatment is to deliver a dose of radiation that destroys tumor cells while limiting the dose of radiation to normal cells. In a typical course of treatment, radiation is delivered five days per week in fractions of the total dose. Depending on the tumor type, stage of disease, and proximity of organs or tissues to which only a limited dose is allowed, the total tumor dose may range from 30 to 70 gray (Gy).
Patients receive radiation therapy for either curative or palliative reasons. Curative treatment is possible for any tumor that has not metastasized (spread beyond the primary tumor to distant locations). Cure is more likely for primary tumors that are small and that respond more readily to radiation than the surrounding healthy normal tissue. In early breast cancer, for instance, an appropriate dose schedule effectively kills residual tumor cells remaining in the breast following surgery with no long-term damage to normal breast tissue. In less favorable circumstances involving localized but radioresistant tumors, such as glioblastoma (a type of brain tumor), patients are given a dose sufficient to shrink the tumor without significantly harming the more radiosensitive normal brain tissue that surrounds the lesion.
Even if metastatic spread of a tumor precludes curative treatment, palliative radiation therapy is often beneficial and improves the quality of the patient's remaining life. Radiation is indicated to alleviate pain from metastases to bone, to control bleeding or obstruction caused by tumor growth, and to control neurological symptoms due to brain or spinal metastases.
As stated above, teletherapy is radiation therapy delivered using an external beam of ionizing radiation. Options include gamma rays (from a radioactive cobalt-60 (Co-60) source) and photons or electrons (from an x-ray generator or accelerator). Linear accelerators and other electron accelerators produce high-energy photon and electron beams for treating patients with cancer. A typical treatment uses two or more photon beams aimed from various angles that intersect at the tumor. Electrons, which have less power to penetrate tissue, are used to treat skin lesions, superficial lymph nodes, and other tumors situated near the surface of the patient.
In addition to "conventional" radiation therapy, experts in radiation oncology have developed several other methods of external beam therapy. Intraoperative radiation therapy (IORT) uses electrons to treat tumors that have been surgically exposed. IORT delivers a single high dose of radiation directly to the tumor after overlying and surrounding tissue have been temporarily moved out the way. IORT is of greatest use for accessible tumors of the abdomen and pelvis that cannot be removed surgically. Stereotactic radiosurgery (SRS) delivers radiation beams to a small target within the skull. The resulting dose distribution yields a small region of high dose precisely conforming to the target. SRS has been proven to be an effective treatment for arteriovenous malformations, and it is being evaluated for treatment of primary and metastatic brain tumors. Dynamic conformal radiation therapy uses a computer to shape the radiation field continuously as the linear accelerator rotates about a patient. In combination with three-dimensional treatment planning, this technology facilitates the treatment of tumors with complex geometric shapes and allows radiation therapy clinicians to increase tumor dose and simultaneously reduce normal tissue dose.
Cancer can be treated in three principal ways: surgery, radiation therapy, and chemotherapy. Surgery and radiation therapy are localized treatments, whereas chemotherapy provides systemic treatment for both local and disseminated disease. The choice of treatment depends upon which modality or combination of modalities offers the patient the greatest chance of cure, the best preservation of normal function and appearance, and the least chance of harmful side effects. Radiation therapy alone, or combined with conservative surgery, generally affords the cancer patient the greatest opportunity for curative treatment with functional preservation. This combination is widely employed for a variety of human neoplasms. Breast cancer and prostate cancer illustrate the points.
Breast cancer. Detection and treatment of early breast cancer is a significant health care issue for the United States. With the advent of effective breast cancer screening programs, more breast cancers are being detected at an earlier stage. The American Cancer Society estimates that about 183,000 new cases of breast cancer will be diagnosed in 1995 (Steele et al., 1994). The functional and cosmetic results of treatment are of significant concern to patients with early breast cancer. Clinical trials have established that breast-conserving treatment, consisting of local tumor excision and radiation therapy, results in a 10-year survival rate equal to that of radical surgery (masectomy). Following limited surgical excision of the tumor (lumpectomy), all remaining breast tissue is treated with radiation to a uniform dose of 45 to 50 Gy. The surgical site is then "boosted" with an additional 10 to 20 Gy delivered with either electrons or an interstitial radioactive seed implant (see discussion of brachytherapy, below). As more clinicians have become aware of these results, in part through the publication of national consensus panel recommendations, the proportion of breast cancer patients treated with this approach has increased. For more advanced breast cancer, radiation therapy also is used to irradiate the chest wall after mastectomy to reduce the rate of local recurrence.
Prostate cancer. Radiation therapy also plays a major role in the treatment of prostate cancer. Screening programs, particularly prostate specific antigen testing, have resulted in a dramatic increase in the number of new cases diagnosed each year. Early-stage prostate cancer can be successfully treated with surgery (prostatectomy), external beam radiation therapy, or radioactive seed implant. Both radiation therapy and modern nerve-sparing prostatectomy maintain potency in 50 to 70 percent of patients. A typical treatment is delivered using four or more radiation beams, intersecting at the prostate. Customized shielding blocks are used to protect nearby uninvolved anatomical structures, such as the posterior wall of the rectum. Depending on the stage of the disease, a total dose of 60 to 72 Gy is delivered at a rate of 1.8 or 2 Gy per day, five days per week, over a period of six to eight weeks. Seven-year survival rates for patients with prostate cancer that has not spread extensively range from 70 to 80 percent for moderately advanced disease to greater than 90 percent for early-stage disease.
Palliative concerns. Radiation therapy also provides effective palliative treatment for patients with various types of cancers. Dose and fractionation schedules are variable, but the typical course of therapy is 30 Gy given in 10 fractions over a two-week period. Approximately 90 percent of patients receive some relief from the pain of bone metastases, and 54 percent receive complete relief. Hemi-body or whole-body photon irradiation is occasionally performed for widespread metastasis of cancer to the skeleton. Widely disseminated bone metastases can also be treated with systemic radionuclides (discussed in connection with therapeutic nuclear medicine, below).
Brain metastases most frequently are treated by irradiating the entire cranial contents, although solitary lesions may be treated with a much higher effective dose by stereotactic radiosurgery. About 80 percent of patients obtain relief of neurological symptoms, and 50 percent remain free from recurrence of brain metastases until the time of death.
Number of treatments by site. Use of radiation therapy in cancer is a major element of health care today. The distribution of radiation therapy treatments by site in the body roughly follows the distribution of cancer incidence, although there are several types of malignancy that are rarely treated using radiation. Shown in Table 2.11 is the estimated number of new cases of cancer by site for 1995, together with a rough approximation of the number of those cases that may receive radiation therapy. In addition, by giving the percentage represented by each site of the total number of new cases treated with radiation, Table 2.11 shows which cancer sites are more commonly treated with radiation.
Estimated Number of New Cancer Cases by Site in 1995.
Overall, approximately 1.3 million new cases of cancer will be identified this year; of these, about 41 percent will receive radiation treatment. In addition to these new cases, previously diagnosed patients who return for relief of the pain or other problems of metastatic disease or for recurrent disease are also treated with radiation therapies. The actual frequency distribution by site is quite variable, because it depends on local patterns of care, the initiation of new treatment protocols, and the retirement of old ones.
Patterns of Care Studies. The ACR, through the Patterns of Care Studies (POCS), has conducted periodic surveys of the status of radiation oncology in the United States. The relatively small number of centers and physicians involved in the specialty of radiation oncology (and the field's exclusive focus on cancer) facilitate in-depth surveys of the patterns of care in clinical radiation therapy. The POCS measure the size and composition of the radiation oncology care delivery system in the United States and document both the process of care and patient outcomes. Over time, the POCS also contribute information leading to changes in process and improvements in outcomes.
The POCS data are valuable in placing radiation oncology in perspective among the cancer treatment modalities. Based as they are on statistically valid samples of the total spectrum of practice in the United States, the numbers can be relied upon to demonstrate what is experienced in the community in terms of tumor response, survival, and complications. Some of these outcomes data are presented later in this section.
Table 2.12 summarizes the results of those surveys that tracked facilities and work load, showing data for selected years between 1975 and 1990. Between 1975 and 1990, for example, the total number of facilities increased by just under 300 while treatment machines rose by more than 1,000. In the same period, the number of new patients rose by nearly 180,000 persons (or about 12,000 a year on average).
Number of Radiation Oncology Facilities, Number of Treatment Machines, and Patient Loads, 1975-1990.
Much of the growth in machines and new patients in this period occurred between 1986 and 1990, and most of this can be attributed to the expansion of freestanding (nonhospital-based) radiation oncology centers. In 1986, approximately 20 percent of facilities were freestanding, whereas just four years later the figure had increased to 27 percent.
The POCS data reported here reflect the level of clinical activity for new patients only. If an average of 20 to 25 treatments per patient is assumed, in 1990 the estimated number of patient-treatments for this group would range between 9.8 million and 12.3 million. Clearly, however, radiation oncology has a considerably greater work load than that. The total number of patients seen per year is the sum of new patients and ''old" patients (previous patients returning for additional treatment). Depending on practice patterns, these prior patients may account for 30 to 50 percent of total patient load. By using the same 20-to-25 treatments per patient assumption, in 1990 the total number of patient-treatments could be estimated to range between 12.7 million and 18.4 million.
One influential result of the sequential POCS is the availability of outcomes data based on a properly balanced sample of the total practice in the United States. These data show overall survival, disease-free survival, recurrence rates, and complications. Taken as a whole, the data illustrate remarkably high survival rates and comfortably low complication rates. Rates, of course, strongly relate to variables such as tumor type, disease stage, and patient age.
Advances in radiation oncology continue to improve a patient's opportunity for long-term survival. For stage I and II cancers of the tongue and floor of the mouth, recurrence rates at the original cancer site have been reduced from 41 percent (when treated with external beam alone) to 26 percent (when treated with interstitial brachytherapy). For women with carcinoma of the cervix, the four-year survival rate increased from 62 to 73 percent; 15 years after the 1973 study, 51 percent of patients with stage I carcinomas are still alive. Not only survival is at issue; radiation therapy of prostate cancer maintains potency in patients at the same rate as state-of-the-art nerve-sparing prostatectomy.
The POCS have also increased knowledge of dose effectiveness. Stage B prostate cancer shows greatest sensitivity to doses between 60 and 70 Gy, with no advantage seen in higher doses. The higher risks associated with doses over 70 Gy, however, may be acceptable to patients with stage C prostate cancer.
Few recent estimates of collective dose to the U.S. population from radiation therapy have been performed. Although such a calculation could be done, it would be of questionable validity and usefulness, for several reasons. Organ weighting factors used to define EDEs are derived for healthy populations exposed to comparatively low (less than a few grays) radiation levels; they do not take into account the effects of fractionated high-level exposure or implications of a population of cancer patients. Thus, collective dose from radiation therapy should not be used to estimate rates of radiation-induced cancer among the patient population that already has cancer.
The incidence of secondary neoplasms following radiation therapy has been extensively reported in the literature. Various types of radiation-induced cancer have been observed to arise both in the treatment area and at distant sites that were irradiated by scattered and leaking radiation. The issue of secondary tumors can be significant in treatment decisions for patients with curable tumors and otherwise long life expectancies. For instance, elevated incidence of in-field sarcoma has been observed 10 years following radiotherapy for breast cancer. Elevated rates of cancer have also been observed in children receiving cranial irradiation for leukemia and in young adults treated for Hodgkin's disease and seminoma. Of course, some chemotherapeutic agents also increase the risk of later malignancy, so choices among therapeutic options are often difficult.
Regulation and control of external beam radiation therapy is analogous to that of diagnostic radiology and nuclear medicine. In NRC states, the federal government regulates cobalt teletherapy (because Co-60 is reactor produced), and the state regulates all other external beam therapy. In Agreement States, the state regulates all external beam therapy.
Typical state laws specify radiation shielding design levels for facility construction, required interlocks, area radiation monitors, warning labels, and access control. Some states may specify qualifications, training, and licensure of equipment operators and (rarely) radiological physicists, as well as content and frequency of accelerator calibrations. The level of oversight varies considerably from state to state, with some states providing inspection by state radiologic health personnel and others simply registering the existence of the facility.
The regulation of cobalt teletherapy is unique: 10 CFR Part 35 sets out detailed requirements for obtaining a license to possess and operate a cobalt teletherapy unit. Because the regulations of Agreement States must comply with NRC regulations, Part 35 essentially regulates all cobalt teletherapy treatments in the United States. The NRC requires that physicians who are authorized users of Co-60 teletherapy machines be board certified or meet several hundred hours of training requirements. A "teletherapy physicist" must be named on the license and meet similar qualifications. Personnel operating the unit must receive annual instruction in radiation protection and emergency procedures.
The QM section of Part 35.32 defines the required components of a valid physician prescription. It also requires a system of double checks for dosimetry calculations; documented institutional validation of computerized treatment planning software; and identification, prior to each treatment, of the patient by two independent methods. If it is discovered that a patient's delivered total dose varies by more than 20 percent (greater or less) from the prescribed dose, the NRC Operations Center in Washington, D.C., must be notified within one calendar day of discovery of the "misadministration" and the event is thoroughly investigated. In addition, the patient and the patient's referring physician must be notified within 24 hours. All NRC-required records, such as dosimetry equipment calibrations, annual and monthly teletherapy calibrations, personnel training, documentation of required checks in patient charts, and investigations of misadministrations, must be available for unannounced on-site NRC inspection.
The FDA regulates equipment design and construction. Because linear accelerators and radiation therapy treatment planning systems are Class III medical devices, their safety and manufacture is controlled by the FDA. Problems with the operation of such equipment, particularly those resulting in an adverse patient outcome, must be reported subject to the Safe Medical Device Act, as amended in 1991.
Malignant neoplasms also may be treated by radiation sources placed within the body. Brachytherapy is the placement of sealed sources of radionuclides (called seeds) either in body cavities (intracavitary brachytherapy) or directly into body tissues (interstitial brachytherapy). Chief among the advantages of brachytherapy compared to other methods is that the highest radiation dose is delivered where it is most needed. Historically, brachytherapy developed before teletherapy, well before optimal sources of external beam radiation were available.
The original method of brachytherapy is now sometimes called "low dose rate" (LDR) brachytherapy. The radioactivity of sources available at the time of brachytherapy's development was such that, to give a tumor-killing dose, sources had to be left in place for days. Because of the low activity, these sources could be handled manually. LDR therapy typically involves tumor dose rates of from 0.3 to 0.6 Gy per hour.
In the past 20 years, techniques have been developed to manufacture high-activity sources that provide dose rates of 1 to 2 Gy per minute. With "high dose rate" (HDR) brachytherapy, a treatment can be completed in a matter of minutes. The high activity of these sources precludes their manual handling. To handle these HDR sources, intracavitary brachytherapy employs applicators (metal or plastic devices inserted into a body cavity) into which the sealed radioactive sources are later inserted, or "afterloaded," by a computerized robotic device. This approach avoids having radioactive sources in the operating room while others are present.
For interstitial brachytherapy, sources are either inserted directly into tissues or are afterloaded into hollow needles or plastic catheters that pierce the tumor. In some cases, seeds are implanted directly into tissues and left permanently. For radiation safety and radiobiological considerations, permanent implants are feasible only with nuclides having a fairly short half-life.
In the early days of brachytherapy, radium-226 (Ra-226) was the only radionuclide available. After World War II, reactor-produced nuclides became available and the use of Ra-226 gradually declined. The radionuclides commonly applied in brachytherapy in the United States today are listed in Table 2.13 in approximate order of prevalence of use.
Some Properties of Radionuclides Commonly Used for Brachytherapy.
Cesium-137 (Cs-137) is used almost exclusively for LDR intracavitary brachytherapy. Iridium-192 (Ir-192) is used both for LDR interstitial implants and as a single high-strength source for HDR treatments. Iodine-125 (I-125) seeds have been used extensively for permanent interstitial implants at a wide variety of sites, particularly the prostate. Recently, palladium-103 (Pd-103) has been developed for use in permanent implants, because its shorter half-life delivers the total tumor dose over a shorter period of time. Gold-198 (Au-198) seeds also are used for permanent implants requiring rapid delivery of the total dose. Strontium-90 (Sr-90) plaques are used to irradiate very superficial lesions, and use of a strontium applicator is confined almost entirely to the treatment of pterygium, a proliferative disorder of the eye.
Brachytherapy is used alone or in conjunction with external beam radiation therapy to treat a wide variety of malignant neoplasms. Perhaps the most prevalent is the use of LDR and HDR intracavitary brachytherapy for treatment of gynecological malignancies. It is most often used as a local boost following wide-field pelvic teletherapy. The brachytherapy boost is delivered in one or more fractions, each of which requires insertion of applicators into the uterus and vagina. Depending on the overall boost dose and the number of fractions, each implant may deliver from 6 to 20 Gy. LDR treatments last a few days, whereas HDR treatments last a few minutes. Because of the high dose rate, the consequences of a mispositioned or lost source are much more severe for HDR treatments.
Selected prostate cancers can be treated by a permanent interstitial implant. This technique involves implantation of 50 or more I-125 or Pd-103 seeds into the prostate. Because the procedure is done by transperineal needle insertion under ultrasonic visualization, open pelvic surgery is not required. A tumor dose of from 100 to 200 Gy (depending on the size of the gland and the activity implanted) is delivered as the radionuclide totally decays. Early clinical results in well-selected cases are similar to external beam radiation therapy and prostatectomy.
Iridium-192 seeds, spaced 1 centimeter apart inside nylon ribbons that can be after loaded into nylon catheters, are used to treat many sites. For example, interstitial implantation in the breast may be used to provide a localized boost dose in breast-conserving therapy. A single catheter, inserted into a partially obstructed bronchus, esophagus, or bile duct, may be used to relieve obstruction. Boost treatment of primary head and neck cancers, particularly of the tongue and floor of the mouth, may be accomplished by iridium seed implantation. A typical treatment involves surgical placement of 5 to 10 catheters inserted through the tumor. Each catheter is loaded with a length of ribbon to provide an appropriate number of seeds for the size of the tumor in the plane of the catheter. A boost dose of 10 to 20 Gy is then delivered in one to two days.
Radiation regulation and control of nuclides used for brachytherapy is similar to that for diagnostic nuclear medicine. Because a majority of nuclides are reactor produced, the regulatory environment is primarily determined by the NRC, with Agreement States following suit. However, accelerator-produced nuclides are regulated by state law. The Department of Transportation sets packaging and labeling requirements for transport of therapeutic radionuclides.
The QM requirements of 10 CFR Part 35, as discussed above with regard to cobalt teletherapy, apply also to brachytherapy (and to therapeutic unsealed radionuclides, discussed below). No treatment may be delivered without a written directive from a physician named on the authorized user list of the facility license; the patient's identity must be confirmed by two independent means before administration; each administration must be carried out in accordance with the directive; and any unintended deviation (misadministration) from the written directive should be identified and reported to the NRC and to the patient, and corrective action should be taken.
The equipment and procedures for HDR remote after loading brachytherapy have been the subject of much regulatory interest. Several incidents of inadvertent patient overdose have been documented, one contributing to the death of a patient, as described in Chapter 1. The NRC recently has published a 60-page collection of current regulations, standards, and guidelines that apply to remote after loading brachytherapy (NRC, 1994). This document integrates statutory requirements of the NRC and FDA with standards and recommendations from international and national organizations such as the ACR, NCRP, American Association of Physicists in Medicine, American National Standards Institute, International Atomic Energy Agency, and National Institute of Standards and Technology.
In contrast to the smaller amount of radioactivity utilized in diagnostic nuclear medicine, larger amounts of radioactivity are intentionally chosen for use in therapeutic nuclear medicine. Therapy in nuclear medicine involves oral, intravenous, or intracavitary delivery of radionuclides in liquid form (sometimes called "unsealed" radionuclides). The radionuclide is chosen with the aim of ensuring that subsequent physiological redistribution will concentrate the radioactivity in the target tissue and, at the same time, reduce the radioactivity in surrounding normal tissues. Radionuclides suitable for use in therapeutic nuclear medicine must either localize in their elemental form (such as iodine uptake in the thyroid gland) or be bound to an appropriate pharmaceutical or antibody. A list of common nuclides used for therapeutic nuclear medicine is shown in Table 2.14.
Radionuclides Commonly Used for Therapeutic Nuclear Medicine.
Following therapeutic nuclear medicine interventions, some radiopharmaceuticals cause the patient's urine, sweat, saliva, and blood to contain a high level of radioactivity. In many instances, patients must be hospitalized for several days to prevent contamination of the public.
Iodine-131 (I-131) is the most commonly used therapeutic radiopharmaceutical, especially for treatment of hyperthyroidism and primary and metastatic thyroid cancer. The NRC has estimated annual use of I-131 for thyroid ablation at 50,000 administrations per year and for thyroid cancer at 10,000 administrations per year.
Intravenously administered radioiodine in the form of meta-iodobenzylguanidine is used to treat neuroblastoma metastases. Monoclonal antibodies frequently are labeled with I-131 for use in radioimmunotherapy. Recent clinical trials of this modality have shown greatest promise for treatment of neoplasms of the circulatory system, particularly B-cell lymphoma. Radioimmunotherapy of solid tumors is more problematic, both in terms of getting sufficient dose to the tumor and in accurately calculating tumor dose.
Other nuclides are less frequently used to treat a wide range of conditions. Intravenous phosphorus-32 (P-32) is effective in the treatment of myeloproliferative disease, particularly polycythemia vera. Pain from cancer metastases to the bone can be eased with intravenous strontium-89 (Sr-89) chloride. Intracavitary therapy employs P-32 or Au-198 colloid to suppress malignant effusions and dysprosium-165 (Dy-165) macroaggregates for radiation synoviorthesis in rheumatoid arthritis. In all of these applications, patient management is closely coordinated to benefit appropriately from the contributions of surgical, medical, radiation, and nuclear medical specialists.
The same regulatory apparatus that applies to radiation used in brachytherapy applies to radiation used for therapeutic nuclear medicine. For the latter, regulations address the fact that with unsealed source administration, the patient becomes a source of radiation and radioactive contamination. Regulations allow patient excreta to be exempt from treatment as radioactive waste. Hence, disposal of I-131-contaminated urine down the sanitary sewer system is allowed. Contaminated hospital items, such as eating utensils and sheets, must be decontaminated, usually by decay in storage, or disposed of as low-level radioactive waste. The patient may not be released until either the activity remaining in the patient falls below defined limits or the exposure rate 1 meter from the patient dips below 0.05 mSv/hr. Personnel working with large quantities of I-131 sodium chloride are closely monitored for exposure and thyroid uptake.
Diagnostic and therapeutic clinical applications of ionizing radiation range from the simplicity of taking a chest x-ray to the complexity of treating a brain tumor. Each of these procedures benefits patients.
Differing clinical applications involve varying risks to patients, but the level of risk has much to do with the process and little to do with the source of radiation. Whether a teletherapy machine contains a radionuclide produced by an NRC-regulated reactor, or by a hospital-owned accelerator, is of small import when calculating risk. Yet, as hinted at in this chapter's radiation regulation and control sections, regulation in the field is split along this less important distinction between sources. Not only is this fractured regulatory system illogical, it is also costly. This is explored in more depth in the next chapter, "Regulation and Radiation Medicine."
ACR (American College of Radiology). Proceedings of the ACR/FDA Workshop in Fluoroscopy . Reston, VA: American College of Radiology, 1992.
Adelstein and Manning. Isotopes for Medicine and the Life Sciences . Washington, DC: National Academy Press, 1995.
Cagnon, C.H., Benedict, S.H., Mankovich, N.J., Bushberg, J.T., Siebert, J.A., and Whiting, J.S. Exposure Rates in High-Level-Control Fluoroscopy for Image Enhancement . Radiology 178:643-646, 1991. [PubMed : 1994395 ]
Conway B.J., McCrohan, J.L., Antonsen, R.G., Rueter, F.G., Slayton, R.J., and Suleiman, O.H. Average Radiation Dose in Standard CT Examinations of the Head: Results of the 1990 NEXT Survey . Radiology 184:135-140, 1992. [PubMed : 1609069 ]
Conway, B.J., Suleiman, O.H., Rueter, F.G., Antonsen, R.G., and Slayton, R.J. National Survey of Mammographic Facilities in 1985, 1988, and 1992 . Radiology 191:323-330, 1994. [PubMed : 8153301 ]
Edwards, M. Clinical Applications of Ionizing Radiation . Paper commissioned by the Institute of Medicine Committee for Review and Evaluation of the Nuclear Regulatory Commission Medical Use Program. June 15, 1995.
Feig, S.A. Estimation of Currently Attainable Benefit from Mammographic Screening of Women Aged 40-49 Years . Cancer 75(10):2412-2419, 1995. [PubMed : 7736383 ]
Johnson, J.L., and Abernathy, D.L. Diagnostic Imaging Procedure Volume in the United States . Radiology 146:851-853, 1983. [PubMed : 6828707 ]
Mettler, F.A., Briggs, J.E., Carchman, R., Altobelli, K.K., Hart, B.L., and Kelsey, C.A. Use of Radiology in U.S. General Short-Term Hospitals: 1980-1990 . Radiology 189:377-380, 1993. [PubMed : 8210363 ]
Mettler, F.A., Christie, J.H., Williams, A.G., Moseley, R.D., and Kelsey, C.A. Population Characteristics and Absorbed Dose to the Population From Nuclear Medicine: United States-1982 . Health Physics 50:619-628, 1986. [PubMed : 3700113 ]
NCRP (National Council on Radiation Protection and Measurements). Report 100: Exposure of the U.S. Population from Diagnostic Radiation . Bethesda, MD: National Council on Radiation Protection and Measurements, 1989.
NRC (U.S. Nuclear Regulatory Commission). Quality Management in Remote After loading Brachytherapy . NUREG/CR-6276. Washington, DC: Nuclear Regulatory Commission, 1994.
Rueter, F.G., Conway, B.J., McCrohan, J.L., Slayton, R.J., and Suleiman, O.H. Radiography of the Lumbosacral Spine: Characteristics of Examinations Performed in Hospitals and Other Facilities . Radiology 185:43-46, 1992. [PubMed : 1523333 ]
Steele, G.D., Osteen, R.T., Winchester, D.P., Murphy, G.P., and Menck, H.R. Clinical Highlights from the National Cancer Data Base: 1994 . CA 44:71-80, 1994. [PubMed : 8124606 ]
Suleiman, O.H., Anderson, J., Jones B, Rao, G.U.V. and Rosenstein. Tissue Doses in the Upper Gastrointestinal Fluoroscopy Examination Radiology 178:653-658, 1991. [PubMed : 1994397 ]
Sunshine, J.H., Mabry, M.R., and Bansal, S. The Volume and Cost of Radiological Services in the United States in 1990 . American Journal of Roentgenology 157:609-613, 1991. [PubMed : 1872247 ]
Tabar, L., Fagerberg, G., Chen, H-H., Duffy, S.W., Smart, C.R., Gad, A., and Smith, R.A. Efficacy of Breast Cancer Screening by Age: New Results from the Swedish Two-County Trial . Cancer 75(10):2507-2517, 1995. [PubMed : 7736395 ]
Wingo, P.A., Tong, T., and Bolden, S. Cancer Statistics, 1995 . CA 45:8-30, 1995. [PubMed : 7528632 ]
The earlier unit was millirem (mrem); 1 mSv = 100 mrem.
In radiographic imaging, the x-rays emerging from the patient are detected by a cassette containing a sheet of film sandwiched between fluorescent intensifying screens. The resulting radiographic image may be thought of as a two-dimensional map of the differential attenuation of x-rays passing through the body. For fluoroscopic imaging, transmitted radiation is detected by an x-ray image intensifier. Radiologists may use a television pickup tube or a 35-millimeter (mm) cine camera to view the resultant image or, for very common procedures, observe the dynamic image on a closed-circuit television monitor. Selected still images may also be obtained. CT imaging relies on x-ray transmission confined to a narrow (1 to 10 mm) strip. Transmitted x-rays are detected by a scintillation or solid-state radiation detector. By rotating the x-ray source around the patient and taking thousands of transmission measurements at many different angles, a digital image can be reconstructed of a tomographic or cross-sectional "slice" of the patient without anatomical structures superimposed upon one another. In a typical procedure, 10 to 50 adjacent slices are obtained. CT images are much sharper than conventional film-screen images because scatter radiation is eliminated, comparatively high doses of radiation are used, and a narrow range of gray shades can be displayed.
"Interventional procedures" seek to treat disease by anatomic manipulation or drug delivery, through a fluoroscopically guided intravascular catheter. Although interventional procedures are therapeutic applications rather than diagnostic, they are mentioned here because they evolved from special procedures. In percutaneous transluminal angioplasty, a small balloon-tipped catheter is used to open blocked arteries mechanically. The analogous procedure for the coronary arteries in the heart is called percutaneous transluminal coronary angioplasty. Other types of catheters, which use heat rather than expansion to open blockages, also are available. Intraluminal thrombolytic therapy uses selective catheterization to deliver clot-dissolving drugs directly to the site of vascular obstruction. Traumatic or congenital bleeding can be treated by embolotherapy, by introducing an artificial clot-forming material, such as surgical gelatin foam, into the specific site of the bleeding.
The data in Table 2.5 are taken from NCRP Report 100: Exposure of the U.S. Population from Diagnostic Radiation (1989), and are based on surveys conducted in the late 1970s and early 1980s by the FDA's Center for Devices and Radiological Health. They represent institutional averages obtained with standard phantoms (except the UGI data, which were obtained from actual patient procedures). Individual exposures can be quite different, depending on actual patient size, technique factors, image receptor speed, and film processing conditions. For this reason, the Joint Commission for Accreditation of Healthcare Organizations requires that typical patient exposures be measured for each institution. Taken as a broad overview, however, it is evident that, even for procedures having high entrance exposure, the effective dose equivalent for most diagnostic procedures is quite low. This is because a given imaging procedure irradiates only a few organ systems, and organ dose is much lower than entrance skin dose.
Although not related to clinical efficacy, an added benefit of a short physical half-life is that it eliminates problems of low-level radioactive waste disposal, because contaminated hospital supplies can be ''decayed in storage" and then disposed of as normal waste.
