What is the difference between Positron Emission Tomography (PET) scan and Computed Tomography (CT) scan in oncology?

PET vs CT in Oncology: Complementary Modalities with Distinct Roles

PET and CT serve fundamentally different but complementary purposes in oncology: PET provides metabolic/functional information about tumor activity using glucose analogs like FDG, while CT provides detailed anatomical/structural information—and modern integrated PET/CT scanners combine both modalities in a single examination to leverage the strengths of each. 1

Core Differences Between PET and CT

Functional vs Anatomical Imaging

• PET imaging detects metabolic activity by visualizing the distribution of positron-emitting tracers (typically 18F-FDG) that accumulate in metabolically active tumor cells due to their increased glycolytic activity 1, 2
• CT imaging provides anatomical detail through cross-sectional X-ray imaging that reveals structural characteristics, tissue density, and precise lesion localization 1
• PET excels at detecting viable tumor tissue based on metabolic activity, while CT excels at defining tumor size, location, and relationship to surrounding structures 2, 3

Diagnostic Accuracy Differences

• PET demonstrates superior sensitivity and specificity compared to CT alone for mediastinal lymph node staging in lung cancer, with negative predictive values equal or superior to invasive mediastinoscopy 1
• PET is significantly more accurate than CT (96% vs lower accuracy) in differentiating benign from malignant pulmonary nodules as small as 1 cm 1
• For detecting distant metastases, PET identifies occult disease missed by conventional CT imaging in 5-29% of patients, with higher rates in more advanced stages 1

The Modern PET/CT Paradigm

Integrated Scanning Technology

• Almost all current clinical PET imaging is performed using combined PET/CT devices that house both scanners in the same gantry, allowing precise co-registration of metabolic and anatomic data 1
• The CT component serves dual roles: providing diagnostic anatomical imaging AND performing attenuation correction plus anatomic localization for PET findings 1
• Integrated PET/CT offers diagnostic advantages over separate acquisitions, including improved lesion localization, consolidated imaging studies, and reduced scan times (typically <20 minutes for whole-body coverage) 2, 3, 4

CT Protocol Variations in PET/CT

Critical distinction: Not all PET/CT scans include diagnostic-quality CT—referring physicians must understand what type of CT was performed. 1

• Low-dose CT (for PET purposes only): Acquired without breath-holding, no IV contrast, lower radiation exposure; used primarily for attenuation correction and anatomic localization of PET findings 1
• Diagnostic CT: Acquired with breath-holding, often with IV contrast, higher radiation exposure; provides fully optimized anatomical evaluation 1
• Many centers perform low-dose CT as standard with PET/CT and add diagnostic CT only when specifically requested, while others routinely combine diagnostic CT with all PET studies 1

Clinical Applications and Staging Impact

Staging Accuracy

• PET/CT changes clinical stage from conventional CT-based staging in 27-62% of NSCLC patients, with up-staging more frequent than down-staging due to detection of unexpected distant metastases 1
• This leads to changes in patient management in 25-52% of cases, primarily converting treatment intent from curative to palliative 1
• For locally advanced breast cancer (stage III), FDG-PET/CT is most helpful when standard imaging results are equivocal or suspicious, with evidence supporting detection of regional nodes and distant metastases 1

Response Assessment

• PET is more sensitive than CT in measuring biological effects of anticancer therapy and can provide early response assessment during treatment 1
• Good prospective evidence documents PET superiority over CT in correctly identifying recurrent lung cancer 1
• For lymphoma, PET/CT has largely replaced separate PET and CT examinations, with studies showing that PET/CT alone (even without IV contrast) provides equivalent information to separately acquired studies 1, 5

Critical Limitations and Pitfalls

False-Negative PET Results

• PET can miss subcentimetric lesions because a critical mass of metabolically active cells is required for detection 1
• Bronchoalveolar cell carcinomas and ground-glass opacities may exhibit little or no FDG uptake even when >1 cm 1
• Approximately 4% of patients with radiographically and PET-normal mediastinum have unsuspected stage I mediastinal disease discovered at surgery 1

False-Positive PET Results

• Inflammatory conditions and granulomatous diseases cause false-positive FDG uptake (specificity only 79% for pulmonary nodules) 1
• Timing is critical: Imaging too early after treatment causes false-positives from inflammatory changes; wait at least 3 weeks post-chemotherapy, preferably 6-8 weeks, and 8-12 weeks after radiation therapy 6
• Equivocal or suspicious PET/CT findings should be biopsied for confirmation when possible and when results would impact treatment decisions 1

Clinical Decision-Making Caveats

• Never preclude potentially curative surgery based on positive PET alone without tissue confirmation, as false-positives may result in missed cure opportunities 1
• Conversely, false-negative PET results may lead to non-curative resections 1
• For negative PET scans in mediastinal staging, invasive confirmation may be unnecessary only when: (1) sufficient FDG uptake exists in the primary tumor, (2) no central tumor or significant hilar disease that could obscure N2 disease, and (3) dedicated PET camera used 1

Practical Algorithm for Modality Selection

When PET/CT is Superior to CT Alone

• Staging and restaging of FDG-avid tumors (lung cancer, lymphoma, breast cancer, colorectal cancer, head/neck cancer) 2, 3
• Characterizing indeterminate pulmonary nodules or equivocal CT findings 1
• Detecting occult distant metastases when conventional staging is negative but clinical suspicion remains 1
• Evaluating treatment response, particularly early assessment during therapy 1

When Diagnostic CT Remains Essential

• Hepatic or splenic involvement assessment requires IV contrast-enhanced CT, as non-enhanced PET/CT has limitations detecting small lesions in these organs 1
• Detailed anatomical planning for surgical resection requires optimized diagnostic CT with IV contrast 1
• Brain metastases evaluation requires dedicated brain imaging, as standard PET has high physiologic brain uptake 2

Radiation Exposure Considerations

• Radiation exposure from diagnostic CT often exceeds that from the PET emission component 1
• Low-dose CT for PET purposes delivers lower radiation than diagnostic CT 1
• Consider whether diagnostic-quality CT is truly needed or if low-dose CT with PET suffices for the clinical question 1