What is the principle of positron emission tomography–computed tomography (PET-CT)?

Principle of PET-CT Scan

PET-CT combines metabolic imaging through positron emission tomography with anatomical imaging from computed tomography in a single examination, detecting positron-emitting radiotracers (most commonly ¹⁸F-FDG) that accumulate in metabolically active tissues while simultaneously providing high-resolution structural localization. 1

Core Physical Principles

PET Component: Metabolic Detection

• PET measures the three-dimensional distribution of positron-emitting radiotracers through detection of emitted photon energy. 1
• ¹⁸F-fluorodeoxyglucose (FDG) is a glucose analogue taken up by cells via glucose transporters (GLUT1,3) and phosphorylated by hexokinase, becoming metabolically trapped within cells. 1
• FDG accumulation is proportional to glucose utilization, which is markedly elevated in most cancers due to overexpression of glucose transporters and increased hexokinase activity. 1
• ¹⁸F is a cyclotron-produced radioisotope with a 109.7-minute half-life that emits positrons, allowing imaging within 3 hours of injection. 1

CT Component: Anatomical Localization

• CT uses a rotating X-ray transmission source and detector system to generate tomographic images based on tissue density variations. 1
• CT provides high spatial resolution visualization of morphological and anatomical structures with resolution less than 3 mm. 1
• The CT component performs attenuation correction of PET data, eliminating the need for traditional ⁶⁸Ge transmission sources and reducing examination time. 2

Functional Integration: Why Combination Matters

Complementary Information

• PET provides metabolic and functional information while CT supplies anatomical detail, creating a hybrid modality that overcomes individual limitations of each technique. 1, 3, 4
• The integrated approach enables precise co-registration of metabolic abnormalities to specific anatomic structures in a single scanning session. 3, 4, 5
• PET-CT differentiates benign from malignant tissue based on metabolic behavior rather than size or morphology alone. 3

Superior Diagnostic Performance

• Combined PET-CT outperforms PET alone, CT alone, and separate visual correlation of the two studies. 3
• Accurate anatomical localization of increased FDG activity may be difficult or impossible with PET alone, particularly outside the brain where multiple degrees of freedom exist between data sets. 4, 5

Clinical Applications Based on Principle

Oncology (Primary Application)

• PET-CT detects cancer through visualization of increased glycolysis in neoplastic cells compared to normal tissue, a capability absent in CT. 3
• The modality is used for detection, staging, restaging, therapy response assessment, and radiation treatment planning. 1
• Quantitative assessment using standardized uptake values (SUV) allows semi-quantitative analysis of tracer uptake. 1

Infection and Inflammation

• Molecular imaging with PET detects metabolic activity of pathological processes through systemic injection of ligand-specific radiotracers that colocalize with targets of interest. 1
• ¹⁸F-FDG PET-CT has high accuracy in detecting prosthetic valve endocarditis and highlighting remote sites of systemic infection. 1

Emerging Applications

• Novel radiotracers beyond FDG (such as ¹⁸F-fluoride for valve degeneration and ¹⁸F-GP1 for thrombus detection) target cellular processes more specific than glucose metabolism. 1, 6

Critical Limitations of the Principle

False-Negative Results

• Subcentimetric lesions may yield false-negative results because a minimum mass of metabolically active malignant cells is required for detection. 3
• Certain tumor types (e.g., bronchoalveolar cell carcinoma) can exhibit little or no FDG uptake despite size >1 cm. 3

False-Positive Results

• Inflammatory conditions, granulomatous diseases, fungal infections, and benign tumors produce increased FDG uptake due to elevated glucose metabolism in inflammatory cells. 3, 7
• With specificity of approximately 79%, positive PET findings require tissue confirmation before definitive cancer diagnosis. 3

Technical Artifacts

• Metallic objects and contrast agents that alter CT image quality can create artifacts in PET images and affect quantitative SUV measurements. 2