Positron Emission Tomography (PET) is a molecular imaging test that provides a functional view of the body, unlike X-rays or CT scans, which primarily show structure. PET scans visualize active biological processes at the cellular level using a radioactive compound known as a radiotracer, which is injected into the bloodstream. The most frequently used radiotracer is Fluorodeoxyglucose (FDG), a substance designed to map the body’s glucose metabolism. Areas showing high FDG activity are consuming more sugar than surrounding tissues, indicating a heightened metabolic state. Clinicians use this metabolic information to help diagnose, stage, or monitor various diseases.
Understanding FDG as a Metabolic Tracer
FDG is chemically engineered to mimic glucose, the primary fuel source for most cells. The FDG molecule is nearly identical to glucose, but one hydroxyl group is replaced with the radioactive isotope Fluorine-18. This structural similarity allows FDG to be transported into cells using the same glucose transporter proteins (GLUTs). Once inside, the enzyme hexokinase phosphorylates the FDG, converting it into FDG-6-phosphate.
Unlike true glucose-6-phosphate, the altered chemical structure of FDG-6-phosphate prevents it from being broken down further in glycolysis. This effectively traps the molecule inside the cell, causing it to accumulate in proportion to the cell’s metabolic rate—a process often called a “metabolic trap.” The trapped Fluorine-18 isotope emits positrons, which the PET scanner detects to generate an image highlighting areas of high glucose consumption.
Interpreting Areas of High FDG Activity
High FDG activity, appearing as brighter spots on the scan, signifies hypermetabolism in the tissue. This increased uptake is most notably associated with malignant tumors. Cancer cells frequently exhibit the Warburg effect, relying heavily on glycolysis and consuming glucose at a much higher rate than normal cells. The intense accumulation of the trapped FDG tracer in these hypermetabolic cells allows the PET scan to detect and visualize tumor tissue.
Non-Malignant Causes of High FDG Activity
High FDG activity is not exclusive to cancer and can be caused by various benign pathological processes. Active infection and inflammation involve the rapid proliferation and activation of immune cells, such as macrophages and lymphocytes. These immune cells are highly metabolically demanding and show increased FDG uptake, which can sometimes be difficult to distinguish from malignant tissue. Common non-malignant causes include abscesses, granulomas, recent surgical sites, sarcoidosis, or vasculitis.
Normal Physiological Uptake
Interpretation must also account for normal physiological uptake in organs that naturally have high baseline glucose requirements. The brain consistently shows the highest FDG uptake because it relies almost exclusively on glucose for energy. Other areas of normal activity include the heart muscle, which shows variable uptake depending on the patient’s diet, and the kidneys and bladder, which accumulate the tracer as it is excreted.
Muscles, particularly skeletal muscles, may show transient high uptake if the patient moved or exercised before or during the scan. Additionally, brown adipose tissue can become metabolically active and show intense FDG accumulation, often seen in the neck, chest, and upper back, especially when the patient is cold. Understanding these normal and inflammatory processes is essential for accurately interpreting the scan results.
Factors Influencing FDG Scan Results
The interpretation of FDG activity is refined using quantification tools, such as the Standardized Uptake Value (SUV). The SUV is a numerical ratio that standardizes the amount of FDG uptake in an area by correcting for the injected dose and the patient’s body weight. While a higher SUV correlates with increased metabolic activity, it is not an absolute diagnostic measure. Clinicians primarily use the SUV to track changes in a lesion over time, such as monitoring a tumor’s response to therapy.
Patient preparation is a major variable that affects scan quality. The most important factor is the patient’s blood glucose level at the time of injection. If the patient has hyperglycemia (blood glucose above 200 mg/dL), the high concentration of natural glucose competes with the FDG tracer for cell uptake. This competition can lead to falsely low FDG uptake in a tumor, potentially causing a false negative result.
High blood sugar can also trigger increased insulin, causing greater-than-normal FDG uptake into insulin-sensitive tissues like skeletal and heart muscle. This alters the tracer’s normal distribution, making the scan difficult to read by obscuring potential lesions. A known limitation is that not all malignant tumors show high FDG activity; certain slow-growing or very small lesions may have low metabolic rates, leading to minimal or absent FDG uptake.