CONTINUING EDUCATION PET Imaging: An Overview and Instrumentation Farhad Daghighian, Ronald Sumida, and Michael E. Phelps Division ofNuclear Medicine and Biophysics, Department ofRadiological Sciences; and Laboratory ofNuclear Medicine, Laboratories of Biomedical and Environmental Sciences (DOE)*, UCLA School ofMedicine, Los Angeles, California gen in many chemical compounds. None of the above This is the first article of a four-part series on positron elements have any isotope which emits a gamma ray emission tomography (PET). Upon completing the article, the suitable for imaging with a gamma camera. Hence, one reader should be able to: (1) comprehend the basic principles of the advantages of PET over SPECT is that it deals ofPET; (2) explain various technical aspects; and ( 3) identify with isotopes of those elements that are the building radiopharmaceuticals used in PET imaging. blocks of biomolecules. BRIEF HISTORY Positron emission tomography (PET) is a rapidly growing AND FUTURE OUTLOOK OF PET technique within nuclear medicine. A radiopharmaceutical Positron imaging began with the two-dimensional sodium labeled with a positron emitting isotope is administered intra­ iodide detector-based scanning devices developed in the late venously or by inhalation to the patient, and the PET scanner 1950s and 1960s by Wrenn et al. ( 4) and Brownell et al. (5). images the distribution of that radiopharmaceutical. It is the Burham and Brownell also developed a dual-headed multi­ only imaging modality capable of providing quantitative in­ detector camera that provided a limited form of"focal plane" formation about biochemical and physiologic processes (J- tomography ( 6). Robertson and Niel took a different ap­ 3). Other techniques like magnetic resonance imaging (MRI) proach and used a "blurring tomography" with a circular and x-ray computerized tomography (CT) generally image array of sodium iodide detectors ( 7). This latter approach was the anatomy or the structure of the body. the positron version of the device Kuhl and Edwards devel­ Positron emission tomography imaging has some unique oped for single-photon emitting radioisotopes (8). features, which can be summarized as follows: A turning point in medical imaging was reached when 1. The effect of gamma ray attenuation in tissue is removed Hounsfield and Cormack developed x-ray computed tomog­ from the PET image in an exact way, thereby making raphy, for which they shared the Nobel prize in 1978. Earlier the image an accurate measurement of the local radio­ positron imaging devices did not employ the principle of isotope concentration (J-3). computed tomography. 2. There are no collimators in front of the PET detectors; The first true positron computed tomography device was therefore the efficiency of PET is much higher than that developed in 1974 by Phelps, Hoffman, Ter-Pogosian and of single-photon emission computed tomography colleagues ( 9). This work was the beginning of a rapid advance (SPECT). (In the gamma camera more than 99% of the in the principles and techniques of PET. For example, Brown­ emitted gamma rays are absorbed or scattered by the ell et al. (10) and Muehllehner et al. (1 1) developed rotating collimators.) multicrystal and dual-head Anger camera PET systems, re­ 3. Most of the organic chemicals found in the body are spectively. Cho et al. (12), Derenzo et al. (13), Bohm et al. made of carbon, oxygen, nitrogen, and hydrogen. The (14), Tanaka et al. (15), and others developed the early first three of these elements have isotopes which emit circular versions of PET scanners. Allemand et al. introduced positrons, "C (ty, = 20 min), 150 (t.;, = 2 min), and 13 N the first time-of-flight PET system ( 16). Many other academic (ty, = 10 min). Auorine-18 C8F) (t•;, = 109 min), a and comercially-based investigators subsequently contributed positron emitting isotope, can be substituted for hydro- to the development of PET. Research PET centers were established throughout North America, Europe, and Asia during the late 1970s and 1980s. This not only increased ·Operated for the U.S. Department of Energy by the University of California under contract #DE-ACOJ-76-SFOOO 12. biologic research with PET, but also increased research into For reprints contact: Farhad Daghighian PhD, Dept. of Medical Physics, developing new labeled compounds, tracer kinetic assay meth­ Memorial Sloan-Kettering Cancer Center, 1275 York Ave .• New York, NY 10021. ods, and improving PET scanners. The mid-1980s were the VOLUME 18, NUMBER 1, MARCH 1990 5 beginning of the growth in technology to miniaturize and TABLE 1. Examples of Clinical PET Procedures simplify cyclotrons specifically for PET. In addition, auto­ mated chemical synthesis techniques for simplifying the rou­ Procedure Clinical Use tine production of labeled compounds were initiated and 1 . Rest/Stress detection of coronary integrated into the cyclotron technology. artery disease. The principles of PET used to measure and image biologic 3 82 ' NH or Rb plus FOG* 1. Determination of cardiac tissue vi­ processes in the living human subject are sound and their 3 ability for selecting patients for re­ value undeniable. The use of PET to perform biochemical vascularization. examinations of patients for clinical management has now 2. Differentiation of iodiopathic from become the motivation to develop a continuing evolution of ischemic cardiomyopathies: Via­ solutions to the practicalities of its use. ble ischemic cardiomyopathies -+ revascularization; iodiopathic car­ diomyopathies -+ transplant. WHAT ARE THE CLINICAL USES OF PET? FOG 1. Detection, grading degree of ma­ Although PET has been a powerful research tool in medi­ lignancy, post-treatment determi­ cine, it has been shown to be a unique and critical diagnostic nation of reoccurrence and treat­ ment efficacy in tumors (cerebral modality for clinical use. This is because it provides unique and systemic). physiologic and biochemical information about the brain, 2. Differential diagnosis of Alz­ heart, and the rest of the body. The origin of disease is heimer's, multiple infarct demen­ fundamentally biochemical in nature. Therefore, to obtain tia and chronic depression. the most accurate diagnoses and most effective treatment, it 3. Localization of seizure focus in adult and pediatric epilepsy for is desirable to know the biochemical status of the organ or surgical resection. organ system in question. 4. Differential diagnosis of Hunting­ The most common uses of PET in clinical studies are ton's Disease. measurement of the metabolic rate of glucose in different 5. Characterization of cerebral dam­ locations of the brain and the heart. These studies can: age and function on cerebral palsy. I. Help the clinician to pinpoint the location of epileptic 1 . Characterization of hemodynamic foci in seizure disorder patients (3). and metabolic deficits, tissue via­ 2. Identify different forms of dementia and degenerative bility, and therapeutic efficacy in diseases (i.e., Alzheimer's, Parkinson's or Huntington's cerebral vascular diseases (e.g., diseases). stroke). 18 3. Identify the pathology of brain tumors and access the F-L-DOPA 1 . Detection of movement disorders viability of the brain tissue and evaluate the viability of and characterization of dopamine deficiencies. the myocardium in patients with cardiac disease (1 7- 1. Bone scans, detection and moni­ 20). toring of therapy in degenerative bone disease. Blood flow to different locations of the brain is quantitated 18 by PET using '50-labeled water (3), and in the heart by 13N­ • F-Iabeled fluorodeoxyglucose. labeled ammonia or 82Rb (20). Cerebral blood flow measure­ ments combined with measurement of the cerebral metabolic a full course of radiation therapy prior to these scans.) The rate of oxygen is an indicator of the physiologic time course, PET scan is performed 40 min after the injection of 18F­ and metabolic consequences of, and recovery from stroke (3). Iabeled fluorodeoxyglucose (FOG), which is an analog of Myocardial blood flow measurements combined with the glucose. The SPECT image is acquired after the injection of information about the glucose metabolic rate aids the clinician zo'Tl. in identifying whether the patient has viable myocardium, In the PET image, the concentration of FOG is high in the which would benefit from revascularization (20). Some ex­ outer layer of the tumor (the dark semicircle around the amples of PET clinical applications are summarized in Table tumor). This specifically indicates the presence of active tu­ I. There are, however, many others that are discussed in the mor cells since high grade tumor cells use more glucose (21). literature. The tissue at the center of the tumor is dead and, therefore, An example of how metabolic information acquired by does not metabolize glucose. In the CT scan, the bright ring PET is an aid to the clinician is shown in Figure I. The CT, around the tumor only suggests that the 888 is disrupted but PET, and SPECT scans of a patient with biopsy-proven high­ not whether there is an active tumor. The SPECT image grade brain tumor is presented. The CT scan, performed after shows an area of increased uptake of 201 Tl, yet provides little the injection of a contrast agent, indicates a disruption of the information about state of the tumor and the surrounding blood brain barrier (888) that can be caused by the tumor, tissues. The information acquired by PET in this case is radiation necroses or edema (3), the specifics of which can important in the future treatment of the patient. Many other not be differentiated by CT or MRI (3). (The patient received examples of how PET and its physiologic and metabolic 8 .JOURNAL OF NUCLEAR MEDICINE TECHNOLOGY nuclei in the surrounding medium (Fig. 2). Eventually, it will collide with one of the many electrons in the medium and spontaneous annihilation takes place: e• + e- --+Gamma + Gamma. All these events are so fast that for all practical purposes the emission and annihilation of the positron can be considered simultaneous.