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In this chapter, different methods of disposal of radioactive waste adopted in nuclear medicine are elaborately discussed, namely, decay-in-storage, disposal into sewage, incineration, and transfer to authorized recipients. Sewer disposal and incineration are restricted by maximum permissible concentration limit allowed by the NRC in the sewer and the air. Transfer of radioactive waste to authorized recipients requires a manifest, which gives the details of shipment such as type and quantity of material, date, etc. Disposal of sealed sources and cadavers with radioactivity is mentioned.

The Department of Transportation regulates the transportation of radioactive materials. Types of packaging, sturdiness of packages, and categories of materials for shipment are discussed.

This chapter addresses the issues of releasing the patients after administration of radiopharmaceuticals. The limits of exposure and activity at which the patient can be released after administration of both sealed and unsealed sources of radioactivity are discussed. When to give instructions to the patients for isolated living to prevent exposure to family members and the public is provided. Recommendations for cessation of breast-feeding after administration of radiopharmaceuticals to breast-feeding mothers are elucidated.

This chapter is an abridged version of NRC 10CFR35 that describes the conditions for the uses of byproduct materials in humans for medical purposes. Issues of license requirement, dosage measurement, calibration of equipment, radiation safety officer, radiation safety committee, and written directives are discussed. Survey meter and measurement of exposure rate are described. Conditions of medical mobile service are spelled out. Medical events are defined and requirements for their reporting are elucidated. Also conditions for reporting the fetal dose are given.

Use of byproduct materials requires authorization by appropriate authorities. The NRC and the Agreement States are the essential authorities to control the use of byproduct materials. Conditions of different licenses for use of different radioactive materials are presented in this chapter. General domestic license, specific license of limited scope, and specific license of broad scope are discussed, and procedure to apply for each type of license is described. The chapter includes a section on accreditation requirements of nuclear facilities by the American College of Radiology (ACR) and the Intersocietal Commission for Accreditation of Nuclear Medicine Laboratories (ICANL).

This chapter describes some special radionuclides which have great potential in nuclear medicine. These radionuclides are divided into two groups: radionuclides that are clinically proven useful and radionuclides that have great promise for future clinical use. This radionuclide has been used primarily for bone marrow imaging, either by positron scintillation cameras or by dual probe rectilinear scanners. The major difficulty with this radionuclide is its high energy gamma radiations of 446 and 511 keV, which are not ideal for imaging with a scintillation camera. Thallium-201 is commercially available carrier-free in the chemical form of thallous chloride. In this monovalent form it behaves like alkali metal ions, and therefore lends itself as a useful radionuclide for various clinical applications including myocardial visualization, tumor uptake, and thyroid uptake. Imaging is performed at rest and during exercise by means of a scintillation camera.

Definition of radiation units and various radiation-related terms are given in this chapter. Sources of radiation exposure and calculation of external radiation exposure and internal absorbed dose are presented in detail. Several pertinent tables related to absorbed doses are included in the chapter. A table includes absorbed doses to different organs from administration of different radiopharmaceuticals to humans. NRC dose limits to radiation workers, the public, minor, and pregnant women are given. Effective dose is defined and explained, and its values from different radiopharmaceuticals are presented in a table.

This chapter highlights the training and experience required of individuals to practice in nuclear medicine and radiation therapy using radionuclides and radiations for the diagnosis and treatment of human diseases. Authorization is offered to individuals based on specialty board certification or by acquisition of required hours of classroom and laboratory training and prescribed years of work experience in the related field. Requirements of authorization of physicians, medical physicists, nuclear pharmacists, radiation safety officers, and associate radiation safety officers are cited.

This chapter describes the basic composition of matter, decay modes of radionuclides, and radioactive decay equations. α-Decay, β−-decay, β+-decay, electron capture decay, and isomeric transition are briefly discussed. Included in the chapter are the interaction of particulate and non-particulate radiations with matter and their attenuation. Photoelectric effect, Compton scattering, and pair production are highlighted. A section on statistics of counting detailing Gaussian distribution and calculation of standard deviation of counts is presented.

Most common instruments for detection and quantitation of radiation are described in this chapter. The principles of construction and operation of ionization chambers, Geiger-Muller counters, dose calibrators, well counters, and liquid scintillation counters are described in detail. Personnel monitoring devices such as film badges, thermoluminescent dosimeters, optically stimulated luminescent dosimeters are elucidated in terms of their function and utilization. A section on neutron detectors is also added.

This chapter describes the deleterious effects of radiation in humans causing cancer and genetic defects that result from DNA and chromosome damage by radiation. Sources of radiation exposure to the US population are given. Acute short-term effects from whole-body radiation are presented. Long-term effects including carcinogenesis and genetic effects are also discussed. The LNT theory for risk estimate from radiation exposure is discussed as opposed to the theory of a threshold for risk. A discussion is in order on the effects of radiation on the embryo and fetus. A pertinent discussion is presented on the risk versus benefit of nuclear and radiological procedures.

This chapter presents information on the clinical uses of diagnostic radiopharmaceuticals in nuclear medicine. The presentation is based on individual organs and common diseases. For each organ, a brief description of anatomy, different radiopharmaceuticals, and techniques employed for imaging is included. For tumors and tissue-specific diseases, the pathophysiology of the disease, radiopharmaceuticals, and imaging techniques used for their detection are given. PET/CT and SPECT/CT are commonly used for imaging and their pros and cons discussed. The mechanism of radiotracer uptake in the organ and tissues is elucidated. Wherever appropriate, relevant data are presented in tables. Appropriate illustrations of images depicting normal and/or disease states in humans are provided in support of the contents in the text. Pertinent questions and references related to the chapter are added at the end.

This chapter details the general principles of labeling of ligands with radionuclides. Different physiological mechanisms that are taken advantage of in radiolabeling and different physicochemical factors affecting radiolabeling are discussed in detail. While general methods of radiolabeling have been elucidated, iodination and 99mTc are elaborately described. Various methods of radioiodination of different ligands for nuclear medicine imaging are detailed. Since 99mTc is a very important radionuclide for nuclear medicine studies, its properties and various chemical reactions involved in 99mTc labeling of many ligands are described in detail. Various oxidation states of 99mTc in labeled compounds are discussed. The basic principles of manufacturing kits for different radiopharmaceuticals are briefly described. A brief section is devoted to preparation of colloidal substances, and also different additives and preservatives that are often added to radiopharmaceuticals to maintain their integrity are discussed.

The instant thin-layer chromatographic method of determining the radiochemical purity of (99m)Tc-tetrofosmin recommended by the manufacturer uses a mixture of acetone and dichloromethane (35:65 v/v) as the solvent and a silica gel (SG) strip as the solid phase. Currently, SG strips are not available commercially and an alternative solid phase is needed. The present study reports that silicic acid strips are an appropriate substitute for SG strips for the chromatographic method using the same solvent mixture but mixed in a reverse ratio (65:35 v/v). The 2 methods yielded similar values (within 1 SD) of radiochemical purity for (99m)Tc-tetrofosmin.

This chapter describes different protocols for a few common PET procedures to provide a general understanding of how a PET study is performed. Four common procedures are described, namely, whole-body PET imaging with 18F-FDG, PET/CT whole-body imaging with 18F-FDG, myocardial perfusion imaging with 82Rb-RbCl, and myocardial metabolic imaging with 18F-FDG. Another PET/CT procedure using 18F-florbetapir for amyloid imaging in Alzheimer’s patients also has been added. The protocols include sequential steps of patient preparation, dosage administration, scanning the patient, processing of the scan data, and finally storage in the PACS system. These generic protocols may vary in the details from institution to institution. Use of CT contrast agents in PET/CT and the limit of glucose loading in myocardial 18F-FDG studies are debatable issues.

PET/CT has become one of the most common and useful modalities for detection and monitoring of treatment of human diseases because of its high diagnostic efficacy and accuracy. PET centers are growing in large number throughout the world as hospitals and outpatient imaging centers are utilizing PET/CT increasingly for patient care. A PET center is a designated area to accommodate one or more PET and/or PET/CT scanners. Smaller facilities normally possess only a single unit of PET/CT and procure their PET radiopharmaceuticals from commercial vendors having a cyclotron facility. These facilities are not likely to be considered as PET centers. Larger and academic institutes have PET centers that are large enough in area to accommodate several PET/CT scanners, one or more cyclotrons and a radiochemistry laboratory. These centers produce PET radiopharmaceuticals in their own cyclotron and use them for both patient care and research. The following is a brief description of the design of a PET center based on the clinical operation of one PET/CT scanner, a radiochemistry laboratory and a cyclotron.

Completion of a nuclear medicine procedure involves many steps that are intertwinedwith one another.Areferring physician orders a nuclear medicine study for a patient after clinical examination. The patient reports to the nuclear medicine department for the study according to the schedule. The study is performed according to the established protocol using specific equipment. The data are processed and used to construct images which are then stored for display on monitors as needed. The nuclear physician retrieves the images from storage and interprets them to diagnose the patient’s diseases. The report on the diagnosis is dictated into a computer, which can be retrieved along with images by the referring physician for making a clinical decision for the patient. The entire sequence of operations in the procedure is depicted by the term workflow that represents each operation much like flow charts. Workflow software has been developed by various vendors to implement all sequential operations of a procedure in an integrated form. The advantage of workflow lies in the management of large imaging data in multiple formats along with the capability of interrelating among different operations. Below is given a description of storage and display of image data in nuclear medicine and the concept of workflow involving multiple operations to complete a study.

This chapter contains the special topics of interest, namely, estimated absorbed dose from 18F-FDG and 82Rb-RbCl, tumor uptake and related SUV, and infusion pump for 82Rb generator. The calculation of SUV is presented and various factors affecting it are briefly elucidated. The method of determining 82Sr and 85Sr breakthrough from the 82Sr–82Rb generator is presented.

Various aspects of NRC regulations, 10CFR20 for radiation protection and 10CFR35 for medical use of radionuclides, are provided. 10CFR20 includes principles and methods of radiation protection, receiving, storing and disposal of radioactive material, occupational dose limits, personnel monitoring, and radiation safety officer. Different pertinent rules and regulations for using PET radiopharmaceuticals in humans are elucidated in 10CFR35. The Department of Transportation (DOT) requirements for transportation of radioactive material and essentials of 18F-FDG distribution by commercial PET facilities are presented.

A major goal of the PET studies is to obtain a good quality and detailed image of an object by the PET scanner, and so it depends on how well the scanner performs in image formation. Several parameters associated with the scanner are critical to good quality image formation, which include spatial resolution, sensitivity, noise, scattered radiations, and contrast. These parameters are interdependent, and if one parameter is improved, one or more of the others are compromised. A description of these parameters is given below.

The detection and measurement of radiation is based on the interaction of radiations with matter discussed in Chap. 1. In gases, ionizing radiations, particulate or electromagnetic, interact with gas molecules to produce positive and negative ions, which are then collected as current or count by the application of a voltage. The amount of ionization is proportional to the amount of energy deposited by the radiation. At low voltages, the ionization is measured as current that is proportional to the amount of radiation. Dose calibrators, pocket dosimeters, and ionization chambers operate on this principle at low voltages (∼ 150 V). At high voltages (∼ 900 V), ions are multiplied in an avalanche of interactions producing a pulse that is independent of the energy and type of radiation. Each event of interaction is detected as a count, and this principle is applied in Geiger–Muller (GM) counters, which are used as radiation survey meters.

Matter is composed of atoms. An atom consists of a nucleus containing protons (Z) and neutrons (N), collectively called nucleons, and electrons rotating around the nucleus. The sum of neutrons and protons (total number of nucleons) is the mass number denoted by A. The properties of neutrons, protons, and electrons are listed in Table 1.1. The number of electrons in an atom is equal to the number of protons (atomic number Z) in the nucleus. The electrons rotate along different energy shells designated as K-shell, L-shell, M-shell, etc. (Fig. 1.1). Each shell further consists of subshells or orbitals, e.g., the K-shell has s orbital; the L-shell has s and p orbitals; the M-shell has s, p, and d orbitals, and the N-shell has s, p, d, and f orbitals. Each orbital can accommodate only a limited number of electrons. For example, the s orbital contains up to 2 electrons; the p orbital, 6 electrons; the d orbital, 10 electrons; and the f orbital, 14 electrons. The capacity number of electrons in each orbital adds up to give the maximum number of electrons that each energy shell can hold. Thus, the K-shell contains 2 electrons; the L-shell 8 electrons, the M-shell 18 electrons, and so forth.

This chapter provides a summary of the FDA regulations that govern the use of PET radiopharmaceuticals in PET, PET/CT, and PET/MR imaging. The essentials of an IND, NDA, RDRC, Exploratory IND, and Expanded Access IND are discussed along with the requirements by 21CFR212 and USP Chapter for compounding of PET radiopharmaceuticals. The certification and training requirements for physicians and technologists in different imaging modalities are elucidated. A brief description of accreditation of PET imaging facilities is presented.

Prospective delineation of viable from nonviable myocardium in patients with coronary artery disease is an important factor in deciding whether a patient should be revascularized or treated medically. Two common techniques — single-photon emission computed tomography (SPECT) and positron-emission tomography (PET)—are used in nuclear medicine using various radiopharmaceuticals for the detection of myocardial viability in patients. Thallium-201 ( 201 TI) and technetium-99m ( 99m Tc)-sestamibi are the common radiopharmaceuticals used in different protocols using SPECT, whereas fluoride-18 ( 18 F)-fluorodeoxyglucose (FDG) and rubidium-82 ( 82 Rb) are most widely used in PET. the SPECT protocols involve stress/redistribution, stress/redistribution/reinjection, and rest/redistribution imaging techniques. Many studies have compared the results of 201 TI and ( 99m Tc)-sestamibi SPECT with those of FDG PET; in some studies, concordant results have been found between delayed thallium and FDG results, indicating that 201 TI, although considered a perfusion agent, shows myocardial viability. Discordant results in a number of studies have been found between sestamibi and FDG, suggesting that the efficacy of sestamibi as a viability marker has yet to be established. Radiolabeled fatty acids such as iodine-123 ( 123 I)-para-iodophenylpentadecanoic acid and carbon-11 ( 11 C)-palmitic acid have been used for the assessment of myocardial viability with limited success. 11 C-labeled acetate is a good marker of oxidative metabolism in the heart and has been used to predict the reversibility of wall motion abnormalities. ( 18 F)-FDG is considered the marker of choice for myocardial viability, although variable results are obtained under different physiological conditions. Detection of myocardial viability can be greatly improved by developing new equipment and radiopharmaceuticals of better quality.

In addition to providing useful clinical information, cardiac output determined during rubidium-82 positron emission tomographic (PET) myocardial perfusion studies can be used in the measurement of absolute regional myocardial blood flow using Sapirstein's method. This investigation was conducted to compare cardiac output values obtained by post-processing data acquired in a list mode PET myocardial perfusion study with those obtained using a technetium-99m-labeled red blood cell method on the same patients. Results from 14 patients showed that cardiac output can be accurately measured simultaneously in a 82Rb PET myocardial study, allowing determination of multiple perfusion and functional parameters of the heart, thus improving the cost-effectiveness of the 82Rb PET study.

All particulate and electromagnetic radiations can interact with the atoms of an absorber during their passage through it, producing ionization and excitation of the absorber atoms. These radiations are called ionizing radiations. Because particulate radiations have mass and electromagnetic radiations do not, the latter travel through matter longer distance before losing all energy than the former of the same energy. Electromagnetic radiations are therefore called penetrating radiations and particulate radiations non-penetrating radiations. The mechanisms of interaction with matter, however, differ for the two types of radiation, and therefore they are discussed separately.

The operation of a gas-filled detector is based on the ionization of gas molecules by radiation, followed by collection of the ion pairs as charge or current with the application of a voltage between two electrodes. The measured charge or current is proportional to the applied voltage and the amount and energy of radiation, and depends on the type and pressure of the gas.

As stated in Chap. 7, the detection efficiency of γ- and x-rays in gas detectors is very low, because these penetrating radiations travel through the low-density gas with little interaction. To improve detection efficiency for these radiations, solid and liquid scintillation detectors with high density are used. These detectors have the unique property of emitting scintillations or flashes of light after absorbing γ- or x-radiations. The γ- or x-rays interact with scintillation detectors via photoelectric, Compton, and/or pair production mechanisms, whereby the detector molecules are raised to higher energy states through ionization or excitation. These high-energy states return to ground states by emitting light photons. The time to reach the ground state is called the scintillation decay time. The light photons produced are converted to an electrical pulse by means of a photomultiplier (PM) tube (described later). The pulse is then amplified by a linear amplifier , sorted by a pulse-height analyzer (PHA), and then registered as a count. Different solid or liquid detectors are used for different types of radiation. For example, sodium iodide detectors containing a trace of thallium (NaI(Tl)) are used for γ- and x-ray detection, whereas organic detectors such as anthracene and plastic fluors are used for β − particle detection.

Positron emission tomography (PET) is based on the detection in coincidence of the two 511-keV annihilation radiations that originate from β + -emitting sources, such as the patient containing β + -emitting radioactivity. Positrons are annihilated in body tissue and produce two 511-keV annihilation photons that are emitted in opposite directions (180°). Two photons are detected in an electronic time interval, called “coincidence time window”, by two detectors connected in coincidence. Conversion of 511-keV photons to light photons in the detector, formation of a pulse by the PM tube, and pulse-height analysis follow the same principles as in conventional gamma cameras. Detectors are arranged in the array of several rings to have the organ of interest in the field of view. Data collected over 360° simultaneously around the body axis of the patient are used to reconstruct the image of the activity distribution in the slice of interest. Because the two opposite photons are detected in a straight line, no collimator is needed to limit the field of view, and the technique is called the electronic collimation.

Radiation hazards to humans are well documented.To minimize their risks, international and national organizations have been established to set guidelines for safe handling of radiations. As mentioned in Chapter 15, the ICRP and NCRP are two such organizations. They make recommendations and guidelines for radiation workers to follow in handling radiations. The Nuclear Regulatory Commission (NRC) and state agencies adopt many of these recommendations into regulations to implement radiation protection programs in the United States. The NRC regulations are published in the Federal Register in the form of the Code of Federal Regulations (CFR). The regulations pertinent to the practices of nuclear medicine are briefly described here.

Digital computers were introduced in nuclear medicine practice in the mid-1960s, but did not become an integral part in both imaging and nonimaging applications until the mid-1970s. In imaging modalities, the computers are used to quantitate the distribution of radiopharmaceuticals in an object both spatially and temporally. Both data acquisition and image processing in scintigraphy are accomplished by digital computers. In nonimaging applications, patient scheduling, archiving, inventory of supplies, management of budget, record keeping, and health physics are just a few examples of what is accomplished with the help of digital computers. Computational capabilities have advanced tremendously over the years and are still evolving, and the utility of a computer is limited only by the limitations of hardware and software.

This chapter gives a description of synthesis and characteristics of different PET radiopharmaceuticals that are clinically used and also those that have potential for human use. 18F-, 11C-, 13N-, and 18O-labeled compounds are described in detail and some structures are illustrated. A description of an automated synthesis box used for PET radiopharmaceuticals along with a schematic diagram is presented. PET radiopharmaceuticals must be highly purified for patient administration, and it is accomplished by high-performance liquid chromatography at the end of synthesis. Prior to release for human use, PET radiopharmaceuticals undergo stringent quality control tests following FDA and USP recommendations, which include radiochemical yield, radiochemical purity, sterility and endotoxin tests, and many others, which are briefly described.