Basic Considerations

Contents
1.1 1.2 1.3 1.3.1 1.3.2 1.3.3 1.3.4 1.4 1.5 1.5.1 1.5.2 1.6 Nuclear Medicine and Molecular Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Historical Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Scientific Basis of Nuclear Medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Atomic Structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Isotopes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Radioactivity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Radiopharmaceuticals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Technical Principles of Nuclear Medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Scope of Nuclear Medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Diagnostic Nuclear Medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Nuclear Medicine Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S ummary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 2 5 5 7 7 8 9 9 9 11 12 12

Further Reading. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1.1 Nuclear Medicine and Molecular Imaging

Nuclear medicine is a relatively new and rapidly changing specialty that depends on the evaluation of function. It is based on examining the regional chemistry of the living human body using radioactivity. Nuclear medicine simply is the medical use of radioactive agents to diagnose and treat patients. Contrary to morphologic or structural modalities of diagnostic radiology such as x-ray computed tomography (CT) scan, nuclear medicine imaging is functional in nature since it depends on functional changes of the disease. It evaluates physiologic changes, metabolism, and more recently molecular alterations. Functional nuclear medicine studies including positron emission tomography (PET) provide useful information that cannot be obtained by morphologic modalities (Fig. 1.1).
A.H. Elgazzar, A Concise Guide to Nuclear Medicine, DOI: 10.1007/978-3-642-19426-9_1, Springer-Verlag Berlin Heidelberg 2011 1

Basic Considerations

Information Modality Structural

Anatomic

Physiologic

Metabolic

Molecular

Functional

Fig. 1.1 Information provided by two main types of imaging modalities

Diagnostically it complements rather than competes with other imaging modalities (CT, MR, US) that depend predominantly on the morphology as it provides different information. The specialty has expanded and changed toward molecular imaging and therapy. Anatomical abnormality is best diagnosed by morphologic modalitys high-resolution examinations. Nuclear medicine studies are optimally utilized when the information sought is primarily physiological and biochemical in nature. These studies have advantages since they: 1. Are noninvasive and contain minimal risk for the patient 2. Have the ability to continuous monitoring over periods of time from several minutes to several hours without excessive radiation dose 3. Provide quantitation when imaging instruments are interfaced to computers 4. Can provide earlier diagnosis since physiological changes usually occur prior to morphological changes

1.2 Historical Background

The road to the current status of development of nuclear medicine imaging goes back to the discovery of x-rays by Roentgen (Fig. 1.2) in the year 1895 which is considered a start of discoveries in the field of ionizing radiation that opened the way for modern applications of radiation in the many fields including medicine. Radioactivity, the basis of physiologic imaging, was discovered in 1896 by Becquerel (Fig. 1.3) which was further refined and defined by Anthony and Marie Curie (Figs. 1.4 and 1.5). This was followed by several developments of morphologic imaging. Ultrasonography (US) was found in the 1950s while CT was in 1970s and MRI in the eighties. Radioactivity has been used in medicine by detecting activity by counting probes and later by imaging scanners and then cameras. Gamma camera was found in 1950s which was developed progressively later on with tomographic capability and multihead detectors (Figs. 1.6 1.8). More recently, Positron emission tomography (PET) signaled the main birth of molecular imaging which was further strengthened by merging morphologic and functional modalities (Fig. 1.9). Functional capability of US along with nanotechnology-based and optical imaging have added to the scope of molecular imaging technology.

1.2 Historical Background Fig. 1.2 Roentgen

Fig. 1.3 Becquerel

4 Fig. 1.4 Pierre Curie

Basic Considerations

Fig. 1.5 Marie Curie

1.3 Scientific Basis of Nuclear Medicine Fig. 1.6 Gamma camera with a single head

Fig. 1.7 Dual-headed gamma camera

1.3 Scientific Basis of Nuclear Medicine

1.3.1 Atomic Structure
Atoms initially were thought of as no more than small pieces of matter. Our understanding that they have an inner structure has its root in the observations of earlier physicists that the atoms of which matter is composed contain electrons of negative charge. While the atom as a whole is electrically neutral, it seemed obvious that it must also contain something with a

6 Fig. 1.8 Triple-headed gamma camera. Note the three detectors (arrow heads)

Basic Considerations

Fig. 1.9 PET/CT

positive charge to balance the negative charge of the electrons. Then it was confirmed that the atom has negatively charged electrons orbiting a central group of particles forming the positively charged nucleus (Fig. 1.10). Like the atom itself, the atomic nucleus also has an inner structure (Fig. 1.10) that can be described as a tightly bound cluster of protons and neutrons. The nucleus consists of two types of particles: protons, which carry a positive charge, and neutrons, which carry no charge. The general term for protons and neutrons is nucleons. The nucleons have a much greater mass than electrons. Protons naturally repel each other since they are positively charged; however, there is a powerful binding force called the nuclear force that holds the nucleons together very tightly. Nuclear binding force is strong enough to overcome the electrical repulsion between the positively charged protons.

1.3 Scientific Basis of Nuclear Medicine Fig. 1.10 Diagram of an atom

Proton

Neutron

Electron

The energy required to overcome the nuclear force is called the nuclear binding energy. Typical binding energies are in the range of 69 million electron volts (MeV) (approximately one thousand to one million times the electron binding force).

1.3.2 Isotopes
Each atom of any sample of an element has the same number of protons (the same Z: atomic number) in its nucleus. Lead found anywhere in the world will always be composed of atoms with 82 protons. The same does not apply, however, to the number of neutrons in the nucleus. An isotope of an element is a particular variation of the nuclear composition of the atoms of that element. The number of protons (Z: atomic number) is unchanged, but the number of neutrons (N) varies. Since the number of neutrons changes, the total number of neutrons and protons (A: the atomic mass) changes.

1.3.3 Radioactivity
A nucleus not in its stable state will adjust itself until it is stable either by ejecting portions of its nucleus or by emitting energy in the form of photons (gamma rays). This process is referred to as radioactive decay. The unstable isotopes lie above or below the Nuclear Stability Curve. These unstable isotopes attempt to reach the stability curve by splitting into fragments, in a process called Fission, or by emitting particles and/or energy in the form of radiation. This latter process

Basic Considerations

is called Radioactivity. The term radioactivity refers to the spontaneous emission of charged particles or photons by an atomic nucleus that is in an unstable status. This event is called a nuclear transformation, decay, or disintegration. Each decay event involves loss of mass or charge. Unstable isotopes, for instance, those that have too many protons to remain a stable entity are called radioactive isotopes and referred to as radioisotopes for short. The term radionuclide is also sometimes used. When this material is coupled with a chemical to carry it to a specific organ (carrier) it is referred to as radiopharmaceutical.

1.3.4 Radiopharmaceuticals
One of the major contributions of nuclear medicine is the development of radiopharmaceuticals. These are drugs that have been synthesized with radioactive components, which allow the drugs to be followed within the human body. Radioactivity also permits researchers to determine how much of the drug remains in the liver and in other organs, and how much is excreted by the kidneys. Since the physiological approach defines a disease in terms of the failure of a normal physiological or biochemical process, the nuclear medicine diagnostic procedures involve four types of physiologic measurement: (a) regional blood flow, transport, and cellular localization of various molecules; (b) metabolism and bioenergetics of tissues; (c) physiological function of organs; and (d) intracellular and intercellular communication. A number of radiopharmaceuticals have been designed and developed over the past four decades to image the function of many organs and tissue. The uptake and retention of radiopharmaceuticals by different tissues and organs involve many different mechanisms such as simple diffusion, active transport, facilitated diffusion, phagocytosis, metabolic trapping, cell proliferation, cell sequestration, and cell migration (Table 1.1).
Table 1.1 Common radiopharmaceuticals used in medicine Radiopharmaceutical Common clinical use (s) Tc99m pertechnetate Tc99m methylene diphosphonate (Tc99m MDP) Tc99m iminodiacetic acid (IDA) derivatives Tc99m macroaggregated albumin particles (Tc99m MAA) Tc99m MAG-3 Gallium-67 citrate Labeled white blood cells Flourine-18 fluorodeoxyglucose (F-18-FDG) Thyroid gland imaging Bone imaging Hepatobiliary imaging Lung perfusion imaging

Mechanism Trapping Adsorption by hydroxyapatite crystals Active uptake by hepatocytes and excretion with bile Blockage of capillaries and precapillary arterioles Tubular excretion Iron containing globulins binding Cell migration Active transport to cells (glucose analogue)

Renal dynamic imaging Tumor and infection imaging Infection imaging Tumor imaging

1.5 Scope of Nuclear Medicine

1.4 Technical Principles of Nuclear Medicine

A radiopharmaceutical is administered to the patient and it accumulates in the organ of interest. Gamma-rays are emitted in all directions from the organ and those heading in the direction of the gamma camera enter the crystal and produce scintillations. A flash of light appears on the screen of the Cathode ray oscilloscope (CRO) at a point related to where the scintillation occurred within the NaI (Tl) crystal. An image of the distribution of the radiopharmaceutical within the organ is therefore formed. The form of imaging, Planar imaging (Fig. 1.11a) produces a two-dimensional image of a three-dimensional object. As a result images contain no depth information and some details can be superimposed on top of each other and obscured or partially obscured as a result. This is also a feature of conventional x-ray imaging. Tomographic images are also obtained using gamma cameras or positron emission tomographic cameras where images are recorded at a series of angles around the patient. These images are then subjected to a form of digital image processing in order to compute images of slices through the patient (Fig. 1.11b). New procedures combine PET or gamma camera with computed x-ray tomography (CT) scans and more recently with Magnetic Resonance Imaging (MRI) to give fusion of the two images (PET/CT, PET/MR and SPECT/CT), and enables better diagnosis than with traditional gamma camera or PET alone. It is a very powerful and significant tool which provides information that cannot be obtained from any of these modalities alone on a wide variety of benign and malignant diseases.

1.5 Scope of Nuclear Medicine

Although nuclear medicine imaging is still widely underappreciated and underused by the medical communities, it continues to provide advances for diagnosis and treatment of many diseases, as well as many fundamental insights into the complex workings of the human body. The vast majority of the specialty is diagnostic while the smaller portion is therapeutic which is expanding quickly.

1.5.1 Diagnostic Nuclear Medicine

Over 10,000 hospitals worldwide use radioisotopes in medicine, and 8590% of the procedures are for diagnosis. The most common radioisotope used in diagnosis is technetium-99, with more than 30 million procedures per year worldwide. Among developed countries, in the USA there are some 18 million nuclear medicine procedures per year among 305 million people, and in Europe about 10 million among 500 million people. In Australia there are about 560,000 per year among 21 million people.

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Basic Considerations

Tc99m MDP

Planar

SPECT

Fig. 1.11 (a) Two dimension (planar image) bone image showing abnormality in the right face (Fibrous dysplasia). (b) Tomographic images of the skull of the same patient showing slices of the skull and more details of the abnormality (arrows)

1.5 Scope of Nuclear Medicine

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Nuclear medicine is used to diagnose many diseases of many organs using unstable agents that emit gamma rays from within the body as they decay. These tracers are generally short-lived isotopes linked to chemical compounds which carry the molecules to desired location which permit specific physiological processes to be scrutinized. They can be given by injection, inhalation, or orally. The photons emitted are detected by a camera which can view organs from many different angles. The camera builds up an image from the points from which radiation is emitted; this image is enhanced by a computer and viewed by a physician on a monitor for indications of abnormal conditions (Fig. 1.12). This specialty illustrates a team model in medical practice since physicians, technologists, radiopharmacists, physicists, radiation safety officer, and computer engineer are needed to practice. For interpretation of images, physicians need the patients medical history, laboratory and radiologic procedures previously done, previous nuclear studies, and perform physical examination when needed.

1.5.2 Nuclear Medicine Therapy

Nuclear medicine offers treatment options for several diseases and this component is expanding rapidly. Examples of the therapeutic applications include thyroid hyperactivity, bone pain due to metastases, certain joint diseases, blood diseases, and tumors as thyroid cancer and lymphomas. The treatment using radionuclides usually consists of a single administration with very few side effects. Rapidly dividing cells are particularly sensitive to damage by radiation. For this reason, some cancerous growths can be controlled or eliminated by irradiating the area containing the growth. External irradiation (sometimes called teletherapy) can be carried out using a gamma beam from a radioactive cobalt-60 source, but the much more versatile linear accelerators are now being utilized as a high-energy x-ray source. Internal radionuclide therapy is by administering or planting a small radiation source, usually a gamma or beta emitter, in the target area. Short-range radiotherapy is known as brachytherapy, and this is becoming the main means of treatment. Iodine-131 is commonly used to treat thyroid cancer, probably the most successful kind of cancer treatment. It is also used to treat nonmalignant thyroid disorders.

Fig. 1.12 Illustration of the technique of nuclear medicine imaging

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Basic Considerations

1.6 Summary
The field of nuclear medicine is an interdisciplinary approach since it interacts with multiple medical specialists. Nuclear medicine has developed in the past 50 years and is now a fully established medical specialty. It depends on the use of unsealed radionuclides and the tracer principle. Nuclear medicine combines medicine and basic biological sciences which originally had their roots in the fields of radiology, internal medicine, and pathology. Although nuclear medicine is primarily a clinical diagnostic discipline, it uses physical-chemical principles and requires a background in such areas as physiology, biochemistry, mathematics, physics, chemistry, computer sciences, and statistics. A wide selection of radiopharmaceuticals is available for single-photon imaging designed to study numerous physiologic processes within the body. Static, dynamic, gated, and tomographic modes of single-photon acquisition can be performed. Dual-photon imaging is the principle underlying positron emission tomography (PET) and is fundamentally tomographic. PET has expanded rapidly due to the clinical impact of the radiopharmaceutical 18F-fluorodeoxyglucose, a glucose analogue used for imaging of malignancy. The fusion of nuclear medicine tomographic images with anatomic CT is evolving into a dominant imaging technique. Nuclear medicine diagnostic procedures yield mainly functional information and contribute to the management of a wide spectrum of diseases. Therapeutic nuclear medicine utilizes targeted radiation damage at the disease site and has applications in both benign and malignant diseases. The future directions for nuclear medicine include increasing use of tomographic methods and the development of radiopharmaceuticals which localize on receptors.

Further Reading
Cember H (2009) Introduction to health physics. McGraw-Hill, New York Cuocolo A, Breatnach E (2010) Multimodality imaging in Europe: a survey by the European Association of Nuclear Medicine (EANM) and the European Society of Radiology (ESR). Eur J Nucl Med Mol Imaging 37:163167 Ernest Lawrence http://en.wikipedia.org/wiki/Ernest_Lawrence Ernest Rutherford http://en.wikipedia.org/wiki/Ernest_Rutherford Henkin RE (2006) Nuclear medicine, 2nd edn. Mosby, St. Louis Henri Becquerel http://en.wikipedia.org/wiki/Henri_Becquerel James Chadwick http://en.wikipedia.org/wiki/James_Chadwick JJ Thomson http://www.aip.org/history/electron/jjthomson.htm Lide D (2001) CRC handbook of chemistry and physics. Boca Raton, London/New York Marie Curie http://en.wikipedia.org/wiki/Marie_Curie Saha G (2001) Physics and radiobiology of nuclear medicine, 2nd edn. Springer, Berlin Wagner HN Jr (2006) A personal history of nuclear medicine. Springer, New York