Diagnostic Applications of 18F-FDG PET/CT in Fever of Unknown Origin

Fever of unknown origin (FUO) remains a diagnostic challenge due to its broad differential diagnosis encompassing infectious diseases, non-infectious inflammatory disorders and malignancies. 18F-fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography (18F-FDG PET/CT) has gained traction as a whole-body imaging modality that detects hypermetabolic lesions indicative of underlying pathology. Its high sensitivity for inflammatory and neoplastic processes enables localisation of occult foci when conventional imaging and laboratory tests are equivocal. Clinical studies report an overall diagnostic yield of around 50–60 per cent, with true-positive findings guiding targeted biopsy or antimicrobial therapy. A normal or negative scan can also be pivotal in excluding focal disease and predicting a benign course. Recent technical advances—including improved scanner resolution, standardised patient preparation protocols and quantitative metrics such as standardised uptake values—have enhanced image quality and diagnostic confidence. Incorporation of 18F-FDG PET/CT into structured diagnostic algorithms can shorten time to diagnosis, reduce invasive procedures and inform clinical management across diverse patient populations.

Research from Nature Portfolio

A large single-centre retrospective analysis of 300 patients with fever or inflammation of unknown origin assessed the contribution of 18F-FDG PET/CT in establishing a final diagnosis. In this cohort, PET/CT was decisive in 54 per cent of cases, with a sensitivity of 80.2 per cent and specificity of 89.8 per cent. The procedure led to new or modified treatment in over 40 per cent of patients. Levels of C-reactive protein and white-blood-cell count were not significantly associated with scan outcome, underscoring the modality’s utility across varying inflammatory states. This study emphasises the role of 18F-FDG PET/CT as a pivotal problem-solving tool when standard work-up fails to identify the cause of persistent fever.

Diagnostic Applications of 18F-FDG PET/CT in Fever of Unknown Origin publication trend

The graph below shows the total number of articles in diagnostic applications of 18f-fdg pet/ct in fever of unknown origin across all publications each year (not limited to Nature Index journals).

Technical terms

18F-FDG PET/CT: A hybrid imaging technique combining positron emission tomography with computed tomography using a radiolabelled glucose analogue to detect sites of increased metabolic activity.

Fever of Unknown Origin (FUO): A clinical syndrome defined by prolonged fever (above 38.3 °C) for more than three weeks without an established cause after standard investigation.

Positron Emission Tomography (PET): A nuclear imaging method that visualises physiological and biochemical processes by detecting gamma rays emitted from positron-emitting tracers.

Computed Tomography (CT): An imaging modality that uses X-rays to generate cross-sectional anatomical images of the body.

C-reactive Protein (CRP): An acute-phase blood protein that rises in response to inflammation and infection, often measured to assess inflammatory activity.

References

1. EANM consensus document on the use of [18F]FDG PET/CT in fever and inflammation of unknown origin. European Journal of Nuclear Medicine and Molecular Imaging (2024).
2. Diagnostic value of F-18 FDG PET/CT in fever or inflammation of unknown origin in a large single-center retrospective study. Scientific Reports (2022).
3. Molecular Imaging of Fever of Unknown Origin: An Update. Seminars in Nuclear Medicine (2022).
4. Diagnostic Value of 18F-FDG PET/CT vs. Chest-Abdomen-Pelvis CT Scan in Management of Patients with Fever of Unknown Origin, Inflammation of Unknown Origin or Episodic Fever of Unknown Origin: A Comparative Multicentre Prospective Study. Journal of Clinical Medicine (2022).