Nuclear Medicine
Chaitanya R. Divgi
I. DEFINITIONS
A. Nuclear medicine is the use of radioactive tracers in the form of unsealed sources for the diagnosis, therapy, and laboratory testing of human diseases. The common radiopharmaceuticals include 25 forms for diagnostic imaging applications and 5 forms for therapy (Table 2.1).
B. Radioactivity, radioisotopes, and radionuclides. The nucleus contains a variety of subatomic particles, such as protons and neutrons, which are held together by incredibly strong short-range forces. The atomic number (Z) of an atom is the number of protons in the nucleus and is characteristic of a particular element. The mass number of an atom is the sum of the protons and the neutrons (A); it is this number that we refer to in this section unless otherwise specified. For most of the common elements in the earth, the nucleus is completely stable and unchanging. Radioactive elements occur when the balance of subatomic particles in the nucleus is inherently unstable. Each radionuclide has specific radioactive decay characteristics in terms of half-life and radioactive emissions.
1. The half-life (t1/2) is the time required for one-half of the atoms to undergo radioactive decay.
a. The half-life of most of the radioisotopes is short, and they therefore do not exist in nature. Some naturally occurring elements are radioactive; for example, 40K accounts for 0.1% of the potassium found within the human body and has a half-life of 1.26 × 109 years. Other naturally occurring radioactive elements include radium, thorium, lead, and carbon. All elements with atomic weights greater than 209Bi are radioactive. The transuranium elements may also have half-lives of 10,000 years or more.
b. Most of the radioactivity used in nuclear medicine is artificially produced in a cyclotron or reactor (see Sections I.D.5 and I.D.6). 131I, for example, has a half-life of 8 days and emits a gamma ray of 364 keV, along with several beta particles, including one with a maximum energy of 0.606 MeV. These radioactive emissions can be detected externally and permit 131I to be useful as a tracer for the study of thyroid physiology.
2. Forms of radioactive emissions
a. Gamma rays: Photoelectric energy that is capable of penetrating a meter or more through human tissue
b. Beta rays: Particulate emissions with the mass of an electron and a negative charge that are capable of penetrating from a few millimeters to about a centimeter in tissue
c. Positrons: Particulate emissions with the mass of an electron and a positive charge that travel for a few millimeters in tissue and then interact with an electron, forming annihilation radiation
d. Annihilation radiation: Two gamma photons of 511-keV energy traveling at 180 degrees from each other that are created when a beta ray and a positron combine
Table 2.1 Some Diagnostic and Therapeutic Radiopharmaceuticals | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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e. Alpha particles: Two neutrons and two protons (a helium nucleus) that are capable of traveling for about 10 to 20 cell diameters in tissues
f. X-rays: Result from rearrangement of electrons in orbit around the nucleus
g. Auger electrons: Low-energy electrons that are emitted from the orbits around the nucleus and travel only a few microns in tissue
h. Applications. Gamma rays and annihilation radiation in particular are useful for various diagnostic imaging applications. The shorter range particles, such as alpha particles, beta rays, and Auger electrons, are used for therapeutic applications.
3. Quantity of radioactivity
a. Becquerel (Bq). One disintegration per second (dps) is defined as 1 Bq of radioactivity, in honor of the discoverer of radioactivity. Typical doses used for imaging are often 37 MegaBecquerels (MBq), which is 1 milliCurie (mCi).
b. Curies (Ci). The curie unit is based on the amount of radioactivity in 1 g of radium or 3.7 × 1010 dps. Typical diagnostic doses range from 1 mCi (37 MBq) to 30 mCi (1,110 MBq).
4. Quantity of absorbed radiation
a. Rads. When radioactive emissions interact with matter, a fraction of the total energy is absorbed. The rad is equivalent to 1 erg of energy absorbed per gram of tissue.
b. Gray (Gy) is the newer unit replacing the rad. One Gray is 100 rad; 1 centiGray (cGy) is 1 rad.
c. Rem (R), or roentgen equivalent man, was introduced as a unit because not all radiation emitted has equivalent potency for the biologic effects that it exerts for a given amount of radiation dose absorbed. For gamma photons and x-rays, the rad dose and the rem dose are the same. For larger particles (e.g., the alpha particle), the rem is the rad dose times a “quality factor.” For alpha particles, the quality factor is much higher, so that for a given rad dose, the rem for alpha-particle exposure is much greater than that for gamma exposure: The exact value is under debate but is typically assumed to be at least 20-fold higher.
d. Sieverts (Sv). One Sv is 100 rem.
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C. How much radiation exposure is safe? The answer is the ALARA principle, which means “as low as reasonably achievable.”
1. In the workplace, a maximum of 5,000 milliRem (mRem) per year is permitted; 25% of this dose (1,250 mRem) is sought. Several decades of exposure of large populations of workers to the 5,000 mR/yr limit has demonstrated no adverse effects. The U.S. Food and Drug Administration (FDA) has used this definition for what could be considered “safe” levels of total-body radiation exposure. Directives for pregnant workers permit 500 mR per 9-month gestational period.
2. The general public in the United States receives an average of 290 mR/yr from naturally occurring radiation. Up to 10 times this exposure may occur at high altitudes, again with no discernible adverse effects. The mandated level for the general public is now set at 100 mR/yr.
3. Diagnostic exposure for the purpose of patient management has no limits because the doses involved are relatively low, and it is generally believed that the benefits outweigh the risks associated with indicated studies.
4. Therapeutic radioisotopes sometimes require admission to the hospital. In the United States, the Nuclear Regulatory Commission has established guidelines such that therapy may be administered on an outpatient basis provided the radiation dose to the general public is within acceptable limits (see above), usually calculated based on the amount and effective residence time of the administered radioactivity; if data are not available for such determination to be made, hospitalization with radiation isolation precautions needs to be carried out until the radiation levels fall to 5 to 7 mR/hr at 1 m from the treated subject. After that point, the patient is not subjected to special precautions.
Photons can set off radiation detectors, increasingly in use in the United States after September 11, 2001. Thus, the patient needs to be advised about the potential for activation of such detectors—most institutions now provide patients with written directives including amount and type of radioactivity received.
D. Instrumentation
1. Well counters. A radiation-sensitive crystal (usually sodium iodide) is fashioned so that a small test tube containing a body fluid can be placed in a well. For each decay, the energy from the emitted radiation is deposited in the crystal, and the crystal is induced to emit a pulse of light. This light pulse is converted to a weak electrical signal by a photoelectric tube. Further amplification results in a signal that can be read as an individual “count.” Typical samples have 10,000 to 20,000 counts per minute (cpm). The amount of the radiotracer present is proportional to the total amount (cpm) detected. By reference to standards of known activity, the absolute amount of tracer can be detected.
2. Gamma camera devices are the most commonly used imaging device for the widely available radiopharmaceuticals, such as 99mTc, 111In, and 131I. The gamma camera is designed as a circular sheet of sodium iodide crystal, encased in a lead shield and directly coupled to 90 or more photoelectric tubes. A collimator device in front of the crystal serves to focus the radiation; it is a 1-in. thick lead shield with holes punched in the lead. Every disintegration in the patient that results in a gamma ray travels to the collimator and passes through the holes in the lead to strike the radiation-sensitive crystal. A light pulse is created in the crystal and is detected by several photomultiplier tubes simultaneously. A computer calculates where the photon hit the crystal,
with the strongest signal being nearest the site where the photon struck the detector. Resolution is about 1 cm or so for most planar gamma cameras.
with the strongest signal being nearest the site where the photon struck the detector. Resolution is about 1 cm or so for most planar gamma cameras.
3. Single photon emission computerized tomography (SPECT). In this form of imaging, radioactivity within the patient is collected at 360 degrees around the patient, and the data are reconstructed into a three-dimensional representation. The data are collected by rotating a specialized gamma camera around a patient who has received an injection of radioactivity that is stable in distribution for the 45- to 60-minute collection times typically required. SPECT is commonly used for the imaging of 67Ga citrate in the mediastinum of patients with lymphoma, 201Tl in myocardial perfusion studies, hemangiomas within the liver, and radiolabeled antitumor antibodies.
The typical in-depth resolution is 16 mm, somewhat more coarse than for planar imaging. Planar gamma camera imaging provides better contrast resolution, whereas SPECT provides better images of small, deep lesions, especially when attenuation correction (whereby radioactivity emitted from deeper in the body is corrected based on the amount and type of tissue between the source and the detector) is carried out, using either assumptions or actual measurements of the density of tissue and nature of the attenuation.
4. Positron emission tomography (PET) has the highest resolution and is the most sensitive imaging device available for nuclear medicine. For reasons related to the physics of positron emission decay, the image can be converted into an accurate, quantitative three-dimensional distribution of radioactivity with a resolution of about 3 to 5 mm in depth within the body. The radiotracers used with PET are 18F, 15O, 13N, and 11C; these elements are readily incorporated into biologic molecules. Most of these radiotracers have half-lives that are too short for shipping. Thus, they must be produced in a hospital-based cyclotron. Nonetheless, clinical applications are emerging, especially using 18F-labeled tracers (which are now commonly being produced by commercial radiopharmaceutical manufacturers). 18F-fluorodeoxyglucose (18F-FDG) imaging of glycolysis by tumors has become the archetypal molecular imaging agent and is increasingly used to diagnose and stage cancer, as well as to demonstrate tumor viability after treatment with radiation or drugs.
5. Cyclotron. The cyclotron accelerates subatomic particles (e.g., protons, deuterons, helium nuclei, alpha particles) to speeds approaching the speed of light. The particle strikes a “target” atom and produces radioactivity. For example, by accelerating protons to about 11 MeV and striking a target that contains an enriched isotope of oxygen (18O), 18F in the form of fluoride ion is produced. These accelerator systems produce a large variety of the radiotracers useful in nuclear medicine, including 11C, 15O, 13N, 67Ga, 111In, 123I, and 18F.
6. Reactors. The reactor is fueled by heavy elements, such as 238U and 235U, which undergo spontaneous fission. Neutrons are emitted from the nucleus and, when present in sufficient quantities, “split” the uranium atoms, with the consequent release of large amounts of energy. An entire cascade of radioactive elements is produced in this process; these elements, called fission products, include 99Mo (from which 99mTc is derived), 131I, 125I, 32P, and 35S. In some cases, a target element is bombarded with neutrons to produce the radioactive element used in medicine (e.g., 89Sr). In other cases, separation of fission products may produce the radioisotope as a by-product of reactor operation (131I, 125I).
II. TUMOR IMAGING STUDIES
A. Bone scanning
1. Indications
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