INTRODUCTION TO MEDICAL MPDs
Medicine was one of the first applications of ionizing radiation as Wilhelm Roentgen himself took an X-ray of a hand within a few days of his discovery in 1895. X-ray tubes became specialized for either diagnostic or therapeutic applications. For diagnostic radiology the tubes had to be designed to handle the high instantaneous energy input from small focal spot tubes, while therapy tubes had to be designed to generate much higher average energy levels for longer periods of time using larger focal spots. To treat tumors at greater depths in the body with external radiation, high-energy accelerators and radionuclide teletherapy units were pioneered in the late 1940s and 1950s. Like X-rays, the radium (Radium-226, 226R) discovered by the Curies in 1898 was quickly used as a therapeutic agent for the treatment of cancer. Radium brachytherapy sources were used for the interstitial treatment of tumors. Newer radionuclides, such as Iridium-192 (192Ir), Palladium-103 (103Pd) and Iodine-125 (125I), have replaced radium for this use. Radionuclides are also used for diagnostic information, as Technetium-99 (99mTc), is commonly used for many nuclear medicine procedures. Historically, the primary measurement laboratories such as the National Institute of Standards and Technology (NIST) played a major role in developing national standards for measuring the radiation used to treat patients. In the 1920s, the free air chamber was designed to measure the then-new radiation quantity “exposure”. Free air chambers with different dimensions were developed to cover the energy range from 10 to 300 keV. In the 1970s graphite cavity ionization chambers were developed to measure the exposure from Cesium-137 (137Cs) and Cobalt-60 (60Co). Recently a wide-angle free air ionization chamber and extrapolation chambers have been used for the measurement of brachytherapy sources, especially those having low energy emissions such as 125I. A recent application of these types of sources is intravascular brachytherapy for preventing or inhibiting restenosis of cardiac vessels. Today, the only traceable units of radiation quantities are Systeme International (SI) units. To enhance patient safety and minimize the risk of errors, the Medical Subcommittee will only accept SI units. Because the role of CIRMS is to deal with measurement and standards, only the use of SI units is acceptable. In particular, the following units should be used for the quantities listed. This is not intended to be a complete list. For the quantity activity, only Becquerels (Bq) shall be used (not Curies, Ci). The Curie is an antiquated unit of activity based on radium. The new SI unit has as its basis the measurable quantity of disintegrations per second. For brachytherapy sources, the quantity expressing output is air kerma strength, having units of energy transferred per unit time at 1 meter distance (Gy-m2/s; Gray-meter squared per second). The unit U = Gy-m2/h is recognized as it is based on Systeme International (SI) units. Apparent activity is likewise not an acceptable quantity; it is based upon the output of a source and only vaguely related to the contained activity because it is dependent on the source geometry.
The national attention to health care and the goal of universal coverage have highlighted the need for cost effectiveness and quality assurance in the care provided to every US resident. Breast cancer is the second leading cause of death by cancer in women. During their lifetimes, one in nine women will develop breast cancer. The Center for Disease Control (CDC) estimates that breast cancer mortality could be reduced by 30% if all women were screened regularly. The best way to prevent deaths from breast cancer is early detection. The best methods of early detection are self-examinations coupled with periodic mammograms. The goal of the Mammography Quality Standards Act (MQSA) was to provide high quality mammograms with the least radiation exposure. When MQSA was passed in 1992 there were no national standards for X-ray tubes commonly found in mammography units. The need for developing mammography air kerma standards was one of the four medical subcommittee Measurement Program Descriptions (MPDs) in the first “CIRMS National Needs Report” (1985). This MPD, the first to be completed, proved highly successful (see Appendix B-2). As a result, national standards are now available for air kerma measurements from molybdenum and rhodium anode X-ray tubes. A network of secondary level laboratories is in place for calibrating the instruments that Food and Drug Administration (FDA) inspectors use in their yearly inspection of mammography facilities, and for calibrating the instruments that medical physicists use in their yearly on-site evaluations of mammography facilities. Most diagnostic X-ray exams are carried out at X-ray potentials between 80 and 120 kV and use filtration typical of the NIST moderately filtered (M) series of X-ray beams. Another MPD was completed so that NIST now offers M80 and M120, as well as molybdenum beams as standard options. A new international standard is in development whereby there will be a new basis for these X-ray beams.
One of the leading causes of death of Americans is cancer — over 25% of the population will die from some form of this disease. Ionizing radiation is one of the common treatment modalities, with over half of all cancer patients undergoing ionizing radiation treatment either for palliation or for cure (approximately 600,000 patients per year). The total cost of these treatments is in excess of $10 billion per year. The goal of radiation therapy is to kill the cancer while sparing normal tissue. This means using large doses of radiation that must be accurately known and precisely delivered to the tumor. Radiation oncologists have been able to detect clinicallyacceptable differences in the responses of patients who experience variations of as little as 5% in the delivered dose. By far the most common types of radiation presently used to treat cancers are beams of X-ray and gamma-ray photons and electrons, although the use of brachytherapy sources is also common for treating some cancers such as prostate cancer. External electron and photon beams are most frequently produced by electron linear accelerators, although radioactive source teletherapy units still play a role for photon treatments. Photon-emitting radionuclides are the primary sources of photons for brachytherapy treatments. A recent application of brachytherapy sources is in intravascular brachytherapy for the prevention of restenosis of coronary arteries. Other types of radiation used include protons, neutrons, and heavy ions. These latter radiations have features that make them desirable for treating some forms of cancer. For example, as protons are slowed down in tissue, they lose more of their energy per unit distance just before they stop. Thus protons can be used to deliver more dose to the tumor and less to the surrounding tissue. Historically, ionization chambers used to measure the output of machines used for radiation therapy were calibrated free in air in terms of exposure (or more recently air kerma) from a 60Co unit. A standard protocol was then used to convert the measurement to absorbed dose to tissue. A more straightforward approach is to calibrate the ion chamber in a water phantom in terms of absorbed dose to water since this is reasonably close to the desired absorbed dose to tissue. Thus, an MPD was included in the 1988 “CIRMS National Needs Report” for developing an absorbed dose to water standard based on a water calorimeter. A water calorimeter was developed, which has allowed NIST to provide an absorbed dose to water calibration factor for ion chambers immersed in water phantoms. An application of brachytherapy radiation is to prevent restenosis following balloon angioplasty. Approximately 40% to 50% of patients having angioplasty experience another obstruction of the arteries within six months. Studies have shown that radiation can slow or eliminate the regrowth of the lining of the injured vessel, delaying or preventing further obstruction. Intravascular brachytherapy involves introducing minute radioactive sources into the artery through a catheter, to deliver radiation directly to the inner surface of the vessel. These sources are in close proximity to the vessels so the determination of the dose at sub-millimeter distances from the source is important. In recent years, drug-eluting stents have largely replaced intravascular brachytherapy as a treatment modality, but the success of brachytherapy was a testament to the careful dosimetry and establishment of standards that supported accurate dosimetry. The need for high-spatial resolution dosimetry in radiation therapy is important not only for brachytherapy, but also for verifying the predicted dose distribution calculated using radiation therapy planning software. Modern treatments given using intensity-modulated radiation therapy (IMRT) particularly demand the ultimate in high-precision dosimetry. With the development of improved methods of implanting brachytherapy sources in a precise manner for treating prostate cancer, there has been a tremendous growth in the use of 125I and 103Pd seeds for this modality. Air kerma strength standards for these brachytherapy sources are developed as new source designs become available, and are subjected to the customary procedures of standardization and comparison. The need for a 103Pd standard as expressed in the 2001 CIRMS Third Report on National Needs in Ionizing Radiation Measurements and Standards has since been met. Therapeutic application of radiopharmaceuticals with curative intent has been practiced since the early 1950s, mainly with Iodine-131 (131I) and Phosphorous-32 (32P). There are presently about 60,000 nuclear medicine procedures performed per year using radionuclides for therapy. There is considerable current interest in the radiation oncology community and the private-sector radiopharmaceutical industry in developing radiolabelled monoclonal antibodies with, for example, the beta-particle-emitting nuclides Yttrium-90 (90Y) and Rhenium-186 (186Re), used in tissue-specific agents for targeting the primary tumor. Finally, an exciting new area is palliative radiopharmaceuticals for use in treating pain associated with bone metastases in the later stages of several types of cancers. It is estimated that up to 125,000 cancer patients per year would benefit from treatment with these bone palliation agents. Some of the nuclides already available or under investigation include 32P, Strontium-89 (89Sr), Tin-117 (117mSn), Samarium-153 (153Sm), and 186Re.
Nuclear medicine, the use of radioactively labeled pharmaceuticals in diagnostic and therapeutic applications, has undergone enormous growth since its introduction in the late 1940s. The needs for radioactive standards used in both diagnostic and therapeutic nuclear-medicine applications continue to be necessary. Diagnostic applications for in vivo imaging have grown to 8.2 million procedures annually in the United States alone. The chief reason for the continued growth is that radionuclides provide physiological information, as opposed to anatomical information (e.g., differences in tissue density) provided by the more common diagnostic X-rays and magnetic resonance imaging (MRI). It has been estimated that over 80% of these diagnostic nuclear medicine procedures involve the use of 99mTc, which has a six-hour half-life. The remaining 20% is accounted for by a score of other gamma-ray emitting radionuclides with half-lives from a few minutes to a few days. Some of the most common procedures include coronary imaging, tumor imaging, renal function studies, and skeletal imaging. Appropriate 99mTc-labeled radiopharmaceuticals have been developed for these and many other applications. A second class of radionuclides used in diagnostic nuclear medicine is the short-lived positron emitters used for positron emission tomography (PET imaging). These include Carbon-11 (11C) with a 20 minute half-life and Fluorine-18 (18F) with a 2 hour half-life, which are ideal because of the ease with which they can be incorporated into biomolecules. The use of PET is growing at a tremendous rate.