Richard L Wahl

Positron emission tomography, PET, is a potent imaging tool in the management of a diverse array of cancers. This chapter briefly discusses the rationale for PET imaging and describes how it differs from more typical anatomic imaging, reviews the principles of metabolic targeting with the radiolabeled glucose analogue 18F-fluoro-2-deoxy-D-glucose (FDG), and then describes the clinical results of PET imaging in several types of common cancers. Although there are detailed descriptions of tumor imaging with other modalities in several areas of this textbook, the discussion here focuses on the role of PET.

PET imaging was originally introduced as a functional tool for quantitatively imaging metabolic activity in the brain. PET is a nuclear medicine technique in which positron-emitting radiopharmaceuticals with short half-lives are injected intravenously into patients and then imaged with a PET scanner. The readers are referred to a textbook that describes in detail the chemistry and physics of positron emission tomographic imaging.1 It should be noted that the most commonly used positron emitter is 18F-fluoride, which is cyclotron produced and has a 109-minute half-life. This radioisotope is most commonly used in clinical PET imaging as 18F-fluoro-2-deoxy-D-glucose (FDG), which traces the early steps of glucose metabolism.

Cancers typically have accelerated glucose metabolism, and FDG traces the initial accumulation of the radiotracer into the cancer via membrane transport, and also its initial phosphorylation by hexokinase to FDG-6-phosphate. This latter substance is polar and typically retained in most cancers.

Glucose utilization is accelerated in most cancers, but some cancers do not have high glucose uptake; these include many prostate cancers, renal cancers (primary), hepatomas and mucinous tumors, and some low-grade lymphomas. Some cancers, such as some brain tumors, that have high glucose uptake may also be difficult to image because the background FDG uptake is high in normal brain. This condition makes defining brain tumors more problematic as the target/background uptake ratios are often lower than elsewhere in the body where there is less normal FDG uptake.

Normal tissues using glucose include the brain, heart, kidneys, testes, exercising skeletal muscle, and the kidneys. FDG is excreted unchanged via the kidneys, which can make detection of lesions in the renal area problematic as well as in the bladder region. PET is a "molecular imaging" tool and, in contrast to single photon emission computed tomography (SPECT) imaging, is capable of providing quantitative data based on the amount of radioactivity in a tissue in the human body noninvasively. It is highly accurate in such quantitation and is able to detect lesions smaller than 1 cm in size. However, PET is not a microscope tool and can often fail to detect lesions in the subcentimeter range. With current available equipment, PET typically loses considerable sensitivity for lesions in the 5-mm range and smaller, but lesion detectability is dependent on many factors, most importantly, the absolute uptake of radiotracer into the lesion as well as the lesion/background ratio. The higher the lesion uptake and the lower the background, the better the chance of lesion detection.

In general, lesions smaller than 5 mm are not detected well with PET in its current form. As a functional imaging tool, PET quantifies the tracer uptake well and displays it in an anatomically correct manner. Unfortunately, if the lesion/background ratio is high, the PET scan can show a "hot spot" but only provide general information as to the precise lesion location. Thus, there has been a great deal of interest in using PET to provide fused images with anatomy, so-called anatometabolic images, which combine form and function into a single image. This merge can be done with software fusion methods, fusing PET and CT or PET and magnetic resonance imaging (MRI) images, but the most common approach is to use dedicated PET/CT scanning devices, which are both PET and CT scanners in a single device.

PET/CT imaging is quickly replacing PET imaging alone as the preferred tool for PET imaging in cancer. This approach was developed by Townsend and colleagues and has been rapidly disseminated throughout the world, with PET/CT scanners representing nearly the entire marketplace for PET imaging equipment at this time. Such devices acquire a CT scan and then a PET scan as part of the same imaging procedure. Because the scanners are linked together, they generate PET, CT, and then PET/CT fused image data. This approach is the new standard for PET imaging of cancer, is the routine procedure for clinical PET at the authors' institution, and is quickly replacing PET alone as an imaging tool. Of interest is that PET alone is a superb imaging tool in many cancers, and PET/CT, while often better and more easily interpreted, is not necessarily dramatically more accurate than PET in all cancers. Nonetheless, PET/CT quite consistently has fewer equivocal diagnoses, fewer equivocal lesion localizations, and greater accuracy than PET. However, much of the evidence for PET is based on the PET literature and is not yet based on PET/CT data. Although only PET/CT images are shown in this chapter, PET imaging represents the foundation for most of the conclusions presented. The use of PET, which has clear advantages over CT or MRI as a functional imaging tool, remains a very valid technique for tumor imaging in clinical practice.

The use of PET has expanded widely in the United States and the world since the approval by the Center for Medicare Services for reimbursement of PET imaging in several common situations. Broadly, Medicare will reimburse for tumor diagnosis, staging, and restaging at present, with more limited reimbursement for PET assessments of early responses to treatment. However, these rules have been in rapid evolution. Currently, the most common uses for PET imaging in our center are for tumor staging, assessment of treatment response, and restaging for recurrence after treatment or with rising serum markers.

The use of PET in several disease types is discussed in detail in the following sections, covering several major types of cancer.

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