Introduction

Introduction

Diagnosing, staging, and re-staging of cancer, as well as the planning and monitoring of cancer treatment, have traditionally relied heavily on anatomic imaging with computed tomography (CT) or magnetic resonance imaging (MRI). These anatomic imaging modalities provide exquisite anatomic detail and are invaluable, especially for guiding surgical intervention and radiotherapy. However, they do have limitations in their ability to characterize tissue reliably as malignant or benign. Anatomic imaging generally has a high sensitivity for the detection of obvious structural alterations (e.g. enlarged structures, abnormal imaging characteristics) but a low specificity for further characterizing these abnormalities as malignant or benign. Necrotic tissue, scar tissue, and inflammatory changes often cannot be differentiated from malignancy based on anatomic imaging alone. In addition, lymph nodes which are not pathologically enlarged by size criteria alone but are harboring malignant cells pose a special diagnostic problem when using traditional cross-sectional imaging.

Therefore, much effort has been forth in the research and development of molecular imaging techniques to detect abnormal behavior of tissues. The nuclear medicine community has developed positron emission tomography (PET) for imaging the activity of an injected radionuclide labeled glucose analogue, Fluorine-18-deoxyglucose (FDG), as a means to discriminate benign from malignant tissues accurately in many clinical settings. This technique is based on the fact that malignant tissue typically exhibits markedly increased rates of glucose metabolism.

Just like glucose, FDG is actively transported into cells mediated by a group of structurally related glucose transport proteins. Once intracellular, glucose (and therefore also FDG) are phosphorylated by hexokinase as the first step in the glycolytic metabolism pathway. Normally, after being phosphorylated glucose continues along the glycolytic pathway for energy production. FDG, on the other hand, cannot enter the glycolytic pathway and becomes effectively trapped intracellularly as FDG-6-phosphate. Tumor cells display increased numbers of glucose transporters as well as higher levels of hexokinase. Most tumor cells are highly metabolically active with high mitotic rates that favor the more inefficient anaerobic metabolic pathway which adds to the already increased glucose demands. These combined mechanisms allow tumor cells to take up and retain higher levels of FDG when compared to normal tissues.

PET provides imaging of the whole body distribution of FDG, thus highlighting the markedly increased metabolic activity of tumor cells. Sites of tumor involvement not obvious from cross-sectional images alone are often found, such as lymph nodes involved by tumor which are not pathologically enlarged by size criteria.

An important concept regarding PET imaging is that FDG is not cancer specific and will accumulate in any areas of high rates of metabolism and glycolysis. Therefore, increased uptake can be expected in all sites of hyperactivity at the time of FDG administration (e.g. muscles and nervous system tissues); at sites of active inflammation or infection (e.g. sarcoidosis, arthritis, pneumonia, etc.); and at sites of active tissue repair (e.g. surgical or traumatic wounds, healing fractures, etc.).

Taking the molecular imaging concept of PET one step further is the combined imaging modality positron emission tomography/computed tomography (PET/CT). PET/CT fuses functional information in the form of PET data and anatomic information in the form of CT data acquired almost simultaneously so that these information sets can be viewed and interpreted together. In PET/CT, both the multidetector CT apparatus and the PET detectors are mounted in the same gantry, one immediately behind the other. Both PET and CT scanning are performed with the patient lying in the same position on the imaging table resulting in optimal correlation of anatomic and metabolic information. For interpretation, the PET data is actually superimposed upon the CT data (co-registration) resulting in improved anatomic localization of normal and abnormal FDG activity. This fusion process has proven beneficial in more exactly localizing tissues involved by tumor. Better co-registration is especially significant in regions of complex anatomy, such as in the abdomen and in the head and neck. More exact localization of the involved tissues results in more accurate staging and more appropriate treatment planning including surgical therapy, radiotherapy, and medical therapy.