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Positron emission tomography is a sophisticated, physiology-based imaging technique that provides information about the function of tissues and organs. Combining PET data with computed tomography or magnetic resonance images provides clinicians with physiological information linked to an anatomical site. This overview discusses the biological principles underlying the technology, PET radiopharmaceuticals, PET imaging facilities, specific imaging applications and reimbursement issues.

Imaging technology has changed rapidly over the last four decades. This is especially true in the area of breast cancer. While anatomic delineation of breast tumors was considered a crowning achievement of the late 20th century, most recently the major focus has shifted toward physiologic and even molecular level tumor detection. The goals of imaging are threefold: (1) the earliest possible detection of primary breast tumors, (2) correlation of imaging results with other clinical parameters to assess disease biology, and (3) accurate staging and follow-up after treatment. Among the newer imaging technologies to be discussed here are digital mammography, computer-aided diagnosis (CAD), power Doppler ultrasound, magnetic resonance imaging (MRI), isotope imaging: methoxyisobutyl-isonitrile (MIBI) and positron emission tomography (PET). Semin Oncol 28:221-228., (Copyright 2001 by W.B. Saunders Company.)

The next generation of medical imaging scanners includes a combo of positron emission tomography and computed tomography--a hybrid that experts say will revolutionize both the practice and business of cancer treatment through faster and more accurate diagnoses. Accelerating the development of PET-CT machines is HCFA's consideration of expanding Medicare coverage of PET for a larger number of cancers.

The origins of positron emission tomography (PET) date back 70 years. Since the 1970s, however, its use has increased exponentially in the fields of neurology, cardiology and oncology. [18F]-Fluorodeoxyglucose (FDG) whole-body scanning is by far the most widely utilised and recognised application of PET in oncology. However, PET is a very versatile and powerful imaging modality capable of helping bridge the gap between the laboratory and the clinic. This article reviews the history and current applications of PET in oncology and then explores some of the newer applications and potential future uses of this versatile technology particularly in the area of cancer research.

Nuclear imaging methods provide noninvasive indexes of myocardial function, perfusion, and metabolism and are well accepted in clinical cardiology. Advances in prevention and treatment of cardiac disease have resulted in decreasing cardiovascular mortality in industrialized nations. The improvement in therapeutic options has increased the demand for diagnostic tests that might guide clinical decision making. Information beyond the pure anatomic characterization of coronary stenoses is required. Nuclear imaging can be used for early detection and monitoring of the severity and extent of disease. The prognostic potential of such functional testing is being increasingly appreciated and used to guide therapy, thereby resulting in improvement of the quality and cost-effectiveness of the workup of patients with cardiovascular disease. Extensive clinical validation has resulted in growing acceptance of these techniques. Furthermore, ongoing improvement of imaging techniques and development of new radiopharmaceuticals will pave the way for disease-specific, molecular-targeted cardiac imaging in the future.

Over the past years, positron emission tomography (PET) with fluoro-2-deoxy-D-glucose (FDG) has emerged as an important imaging modality. In the thorax, FDG-PET has been shown to differentiate benign from malignant pulmonary lesions and stage lung cancer. Preliminary studies have shown its usefulness in assessing tumor recurrence, and assisting in radiotherapy planning. FDG-PET is often more accurate than conventional imaging studies, and has been proven to be cost-effective in evaluating lung cancer patients. This review will discuss the current applications of FDG-PET as compared with conventional imaging in diagnosing, staging, and following patients with lung cancer.

Microgravity environment induces significant pathophysiological changes in humans. As long-term space habitation and interplanetary missions become commonplace in the next century, researchers and imaging specialists must embrace the unique challenges of microgravity research in developing innovative uses of imaging technology. Microgravity results in cephalad fluid shift, loss of electrolytes, loss of muscle and bone mass, anemia, reduced immune response, variability in gastric emptying and hepatic metabolism, increased bowel transit, and development of space motion sickness. Medical imaging is uniquely capable of assessing all of these physiologic adaptations to weightlessness. The imaging information will also aid in identifying those changes which are potentially beneficial and those which are harmful to humans living in space. Interventions may then be employed to capitalize on the benefits and prevent the harmful effects. This article reviews the physiological adaptations to weightlessness and outlines ways in which medical imaging techniques may provide insight into these adaptations.

Positron emission tomography (PET) is a nuclear medicine imaging tool that has expanded from its vital role in basic research into clinical medicine. This noninvasive diagnostic modality is used in cardiac perfusion and viability; in neurologic conditions such as epilepsy, dementia, and tumor; and in a wide range of common cancers to diagnose, stage, and monitor therapy. The importance of PET in clinical practice is growing rapidly, and the number of PET centers across the country is increasing. It is imperative, therefore, that physicians are familiar with PET, and know where this tool can be the most useful and cost-effective modality for patient management.

The past several years have seen dramatic changes in imaging of the head and neck. Technical improvements in CT and MRI coupled with their widespread availability have made cross-sectional imaging an important adjunct in evaluation of patients with disease of the extracranial head and neck. The most recent advances in head and neck imaging are from new metabolic and functional imaging techniques. The intent of this report is to provide an update on the potential role of positron emission tomography, new MRI agents, and magnetic resonance spectroscopy for evaluating squamous cell carcinoma of the extracranial head and neck.

In the future, we will see continued advancements in all areas of head and neck radiology. Because of the rapid pace of developments in the areas of metabolic and functional imaging and gene therapy, it is likely that currently unsuspected and unknown future applications will also fall within the purview of radiologists. It is imperative that our specialty increase our investment in areas of investigation that were once believed to be outside the realm of imaging. Only then will be able to maintain our participation in multidisciplinary investigations that use imaging-based techniques.

In this review we provide a conceptual overview of radiopharmaceuticals containing positron-emitting isotopes, not a catalog of radiopharmaceuticals or details of syntheses. We hope to provide an integrated framework for understanding the radiopharmaceuticals that are available at this time, describing both their strengths and weaknesses, and to look forward to some of the improvements that might be anticipated in the next decade. The range of biology that can be studied with positron emission tomography (PET) radiopharmaceuticals has greatly expanded, involving more sophisticated tracers and more sophisticated data analysis. PET measurements now encompass increasingly more specific aspects of human biochemistry and physiology as described in this review. As the biology being studied becomes more complex, the demands on the radiopharmaceutical and the methods of data analysis also become more complex. New synthetic chemistry and data analysis must develop in tandem. Radiopharmaceuticals must be designed to ensure that the rate determining step that is of interest is the one reflected in the data from the radiopharmaceutical. The challenge to the PET community of chemists, biologists, and physicians is to apply new knowledge of human biochemistry for developing and validating useful PET radiopharmaceuticals that will, in turn, produce useful nuclear medicine procedures. Initially the synthesis of a compound containing a short-lived radionuclide was a triumph in itself. However as the science advances the radiochemical synthesis becomes just the first step in a long trail that terminates in the compound being used to provide data on biological processes via a well-designed PET experiment. The resulting list of compounds and experiments should be as diverse as all of human biology and pathophysiology.

Techniques such as positron-emission tomography, single-photon-emission computed tomography, functional magnetic-resonance imaging and magnetoencephalography permit the observation of biological processes in the brain in a noninvasive manner. They have yielded new insights into the biological interrelations of sensory, motor and cognitive functions, as well as into brain diseases. Combined use of these techniques may provide more information than just the sum of its constituents, and this may narrow the gap between the biological data provided by these techniques and the mental models described by clinicians, mathematicians, psychologists and philosophers.

This review article forecasts developments in nuclear medicine instrumentation which are on the horizon. Special attention is paid to the physical properties of detectors and multiple-processor parallel processing systems needed for fast and high-quality imaging in emission tomography. Advances in detector technology will improve imaging resolution below 5 mm and will increase sensitivity and quantitative accuracy. In addition, high count rate list-mode acquisition enables 'true' four-dimensional data-sets. A sandwich-like construction of two different crystals allows the simultaneous use of conventional tracers and positron tracers (multiple emission tomography, MET). Transmission-based attenuation and scatter compensation with fast iterative reconstruction methods will further improve image quality. The clinical and scientific importance of improved images and the limits on advances in instrumentation are also reviewed.

New developments in the field of nuclear cardiology include attenuation, scatter and depth resolution correction, newly designed gamma cameras, newer tracers, and newer stress agents. These developments, together with many new applications, are likely to continue to place nuclear cardiology in the mainstream of management of cardiac patients.

Over the past 2 decades we have witnessed an explosion of new radioisotopic tracers aimed at detecting, staging and eventually treating tumors. In fact, nuclear oncology has evolved into a field on its own. Aside from aspecific radioisotopic tracers such as thallium 201 or gallium 67, clinicians and oncologists can now use specific radiolabeled monoclonal antibodies and metabolic tracers. In the near future, molecular probes based on the sequencing of the human genome with an exquisite specificity should also become available. In this article, we shall review the most recent developments in this new field.

The use of radionuclides for medical and for a multitude of other basic research applications has continued to grow at a very rapid pace. Procedures, based on their use as radiotracers for nuclear medicine imaging and for radiotherapy of cancer and other pathology, have become firmly established as important clinical modalities. It is estimated that on an annual basis in the United States alone, radionuclides are used medically in over 13 million imaging procedures, in over 100 million laboratory tests, and in an ever increasing number (> 100,000) for therapeutic administrations. One out of every four hospital patients undergoes a procedure that involves the use of radionuclides. Diagnostic imaging methods using planar/single-photon emission computed tomography and positron-emission tomography (PET) imaging, as well as the measurement of in vivo organ function, physiology, or biochemistry, have become indispensable tools in patient workup and management. More than 80% of all imaging studies (mostly anatomic) currently use technetium-99m (99mTc), because it has turned out to be the ideal isotope from various considerations. However, over the past few years, nuclear medicine has experienced a slow but steady evolution towards functional studies, quantitative PET imaging, and novel therapeutic approaches. New radionuclides are required for these applications, and their development has attracted considerable interest. This article reviews the current status and future prospects for the development of many new potential isotopes. Practical issues, such as the feasibility of large-scale production and wide-spread availability in a continuous reliable fashion, are addressed. To date, the data are not sufficient to answer the question as to whether any of these radionuclides (or their applications, for that matter) will eventually assume as broad-based a role as that of 99mTc. Nonetheless, there are a number of promising radionuclides that could assume an important place in the future practice of nuclear medicine.

In small-cell lung cancer (SCLC), CT scan remains the most accurate imaging modality for evaluating local extension and specific sites of metastatic disease. The role of nuclear medicine in the work-up of SCLC is still limited to the detection of bone metastases. Recently, a new potential diagnostic tool has been introduced based on the presence of somatostatin receptors in SCLC. With the use of radiolabelled somatostatin analogues it is hoped that an equally effective but simpler staging system has been found that gives a better separation of prognostic subgroups. This article reviews the role of nuclear medicine in general and somatostatin receptor scintigraphy in particular in the imaging and staging of SCLC. Clinical value in terms of sensitivity and specificity is discussed in relation with other imaging and staging modalities.

With the development of noninvasive tomographic imaging techniques, it is now possible to measure local chemical and physiologic functions in various body organs. Studies of local cerebral glucose metabolism in infants and children using positron emission tomography (PET) have provided important information on human brain functional development and plasticity. The clinical application of functional neuroimaging techniques in the management of pediatric neurologic disorders has yielded encouraging results. In children with intractable epilepsy being considered for surgical intervention, PET is highly sensitive in localizing focal areas of cortical dysplasia, heterotopias, and other migrational defects corresponding to surface electrographic localization of epileptogenic regions. Expanding PET technology provides a new approach that holds great promise in the diagnosis and management of brain disorders in children.

Positron emission tomography (PET) was initially developed as a research tool for evaluating normal and abnormal physiology. Subsequently, the potential clinical utility of PET was recognized, and several specific clinical indications have been defined. PET has been demonstrated to be clinically useful in evaluating certain disorders of the brain and heart. PET holds significant promise for use in the evaluation of psychiatric illness and in multiple aspects of evaluation of malignancy. A major limiting factor for the growth of clinical PET is the absence of policies for reimbursement by third-party payers. Although rubidium-82 chloride is approved by the Food and Drug Administration (FDA), the lack of FDA approval of fluorine-18 2-fluoro-2-deoxyglucose (FDG) is hampering reimbursement for PET studies. The jurisdiction of the FDA over cyclotron-produced PET radiopharmaceuticals synthesized and used on site is a matter of debate because these drugs are not introduced into interstate commerce and because these activities appear to be permissible under certain exemptions in the Federal Food, Drug, and Cosmetic Act relating to the practices of medicine and pharmacy. The jurisdictional authority of the FDA in regulating these radiopharmaceuticals would be established with certainty only through litigation, but no individual or organization has elected to challenge the FDA at this time. The Institute for Clinical PET (ICP) is developing a Drug Master File that can be used in support of site-specific New Drug Applications (NDAs) for cyclotron-produced radiopharmaceuticals by any organization desiring an NDA. The ICP is optimistic that this method of obtaining FDA-approval of FDG and other cyclotron-produced PET radiopharmaceuticals will be successful and beneficial to sites using PET clinically.

The physical principle of PET is discussed, and its advantages compared with SPECT are presented. Starting from the status of PET today, future developments are discussed with special reference to three-dimensional acquisition and reconstruction.