When does Standardized Uptake Value (SUV) in Positron Emission Tomography (PET) scans not increase?

When SUV in PET Scans Does Not Increase

SUV does not increase in several critical clinical scenarios: when there is successful treatment response, in necrotic or fibrotic tissue, in low-grade or indolent tumors, with certain benign conditions, and when technical factors compromise accurate measurement.

Clinical Scenarios Where SUV Remains Low or Decreases

Treatment Response and Disease Resolution

• Successful therapy leads to decreased SUV values, which indicates positive treatment response rather than therapy failure 1
• In multiple myeloma, complete metabolic response is defined when uptake in previous hot focal lesions decreases to less than liver uptake or becomes unmeasurable 1
• Greater than 25% reduction in tracer uptake corresponds to therapeutic response in meningiomas treated with peptide receptor radionuclide therapy 1
• In oncology, diminishing uptake indicates positive response to treatment, while increasing intensity suggests therapy failure 1

Necrotic, Fibrotic, or Post-Treatment Changes

• Treatment-related changes such as radionecrosis and scar tissue demonstrate low or absent FDG uptake, allowing differentiation from recurrent disease 1
• Necrotic tumor tissue lacks metabolic activity and therefore shows no increased SUV, even when viable tumor is present elsewhere 1
• Post-radiation changes typically show minimal to no tracer uptake compared to active recurrent disease 1

Low-Grade and Indolent Malignancies

• Rare meningioma cases present with low uptake (SUV < 2.3 or SUVRSSS < 3) despite being malignant, though this excludes meningioma with high probability 1
• Low-grade tumors may demonstrate SUV values below diagnostic thresholds, making them difficult to distinguish from benign processes 1
• Indolent disease detected by CT screening may show very low SUV values (≤2.5), which paradoxically correlates with 100% 5-year survival in lung cancer 2

Normal Physiological Tissue

• Healthy brain parenchyma in the contralateral hemisphere shows consistently low baseline uptake, serving as reference tissue for tumor-to-background ratios 1
• Normal liver uptake remains stable and serves as a reference standard for determining pathological uptake in various malignancies 1
• Mediastinal blood pool maintains consistent low uptake, used as a comparator for defining pathological bone marrow involvement 1

Technical Factors Preventing SUV Increase

Measurement and Timing Issues

• SUV accuracy depends critically on proper timing, with standardized protocols requiring approximately 60 minutes post-injection before scanning 1
• Partial volume effects cause underestimation of SUV in lesions smaller than 2.5-3 cm, where background tissue dilutes the signal 1
• Improper normalization to body mass can mask true metabolic activity, particularly when total body mass is used instead of lean body mass 1

Scanner and Protocol Variability

• Different reconstruction algorithms and scanner settings can suppress apparent SUV values, though standardization protocols minimize this effect 1
• Test-retest variability can reach ±30-40% in multicenter studies, meaning apparent lack of SUV increase may reflect measurement error rather than true biology 1
• Gibbs artifacts from point-spread-function reconstructions can create quantitative errors that vary with tumor size and scanner model 1

Biological and Physiological Interference

• Iodine contrast administration suppresses radioiodine uptake in thyroid tissue, preventing SUV increase in I-131 studies when contrast timing is inappropriate 3
• Brown adipose tissue activation requires specific cold exposure protocols; without proper activation, SUV remains at baseline despite tissue presence 1
• Shivering within 60 minutes before or after tracer injection can alter biodistribution, preventing expected SUV increases in target tissues 1

Important Clinical Caveats

Interpretation Pitfalls

• Visual assessment alone can be misleading—semi-quantitative analysis with SUV or tumor-to-background ratios is essential for accurate interpretation 1
• Heterogeneous uptake patterns may show areas of high and low SUV within the same lesion, requiring careful region-of-interest placement to avoid sampling error 1
• Mixed responses can occur where some lesions show increased SUV while others decrease, complicating overall treatment assessment 1

Context-Dependent Thresholds

• SUV thresholds vary by tumor type and tracer used: meningiomas use 2.3 for [68Ga]Ga-DOTATATE 1, while lung cancer prognostic cutoffs may be 10.8 for FDG 4
• Reference tissue selection critically affects interpretation—brain tumors should not use contralateral brain for meningiomas but should for metastases 1
• Timing of assessment matters: early post-treatment scans may not yet show SUV decrease despite effective therapy** 1