Infection and Inflammation in FDG-PET Imaging

Mechanism and Clinical Impact

The American College of Radiology states that FDG uptake reflects glucose metabolism, which is elevated not only in malignant lesions but also in activated immune cells responding to infectious and inflammatory processes 1, 2
False-positive PET results occur most commonly from infectious and inflammatory lesions, and less frequently from sarcoidosis and rheumatoid nodules, according to the American College of Radiology 1
The specificity of FDG-PET/CT for differentiating benign from malignant lesions drops dramatically in regions with high prevalence of infections—as low as 25% in areas with endemic tuberculosis, as reported by the American College of Radiology 1, 3

In non-endemic regions, FDG-PET/CT specificity for pulmonary nodules is 77% (95% CI, 73%-80%), but this decreases to 61% (95% CI, 49%-72%) in endemic infectious disease regions, according to the American College of Radiology 1

The American College of Radiology found that while one study in a coccidioidal endemic region found all nodules with SUVmax >5.9 were malignant, there was significant overlap below this threshold, with sensitivity of only 69% at this cutoff 1
The intensity of FDG uptake itself (SUV or target-to-blood pool ratio) has not been shown to reliably differentiate infection from inflammation or malignancy, as stated by the American College of Cardiology 2

The American College of Cardiology states that FDG uptake pattern provides better discrimination than SUV alone: focal uptake suggests infection while homogeneous uptake along a region suggests aseptic inflammation 2
Visual assessment by experienced readers often outperforms strict SUVmax cutoffs, achieving sensitivity of 96-100% and specificity of 76-86%, according to Praxis Medical Insights 3, 4

Spine infections demonstrate increased FDG uptake with elevated SUVmax values, with FDG-PET/CT showing 94.8% sensitivity and 91.4% specificity for spinal infection, as reported by the American College of Radiology 5, 6
Tuberculous spondylodiscitis shows significantly higher median SUVmax (12.4) compared to pyogenic spondylodiscitis (7.3), though overlap exists, according to the American College of Radiology 6, 7

The American College of Radiology advises to never assume elevated SUV indicates malignancy in regions with endemic infections—tissue diagnosis becomes critical regardless of SUVmax value 1, 3
The European Association of Nuclear Medicine recommends avoiding FDG-PET/CT within 2-3 months after radiation therapy due to radiation-induced inflammation, and waiting at least 6 weeks after surgery due to postsurgical inflammation 8
Recent chemotherapy (within 10 days) and growth factor use (within 2 weeks) can cause false-positive results from bone marrow activation, as stated by the European Association of Nuclear Medicine 8
In patients with cardiac device infections, focal FDG activity higher than liver intensity is more likely infection, but SUV alone cannot reliably differentiate infection from inflammation, according to the American College of Cardiology 2