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Background: [ 18 F]FDG-PET/CT is one of the most important diagnostic techniques in the work-up of patients with fever of unknown origin (FUO)/inflammation of unknown origin (IUO). Little is known on how to optimize the diagnostic value of [ 18 F]FDG-PET/CT in patients with FUO/IUO., Methods: Retrospective study in all patients who underwent [ 18 F]FDG-PET/CT during the work-up of FUO/IUO in a tertiary expert center between 2005 and 2014. Data were extracted from medical records., Results: One hundred and four patients were identified, of whom 68 had a final diagnosis (65.4%). Mainly infections (30.8%) and non-infectious inflammatory diseases (30.8%). [ 18 F]FDG-PET/CT contributed to the final diagnosis in 47 of the 68 patients (69.1%). In 21 patients [ 18 F]FDG-PET/CT did not help making a diagnosis. In ten of these patients [ 18 F]FDG-PET/CT was performed while body temperature, CRP and ESR were normal or unknown. Sixteen of 104 patients underwent repeated [ 18 F]FDG-PET/CT. The second scan contributed to the final diagnosis in five of these patients. In two of these patients, the first scan retrospectively was truly non-contributory. In both patients the first [ 18 F]FDG-PET/CT was made while CRP/ESR was low and fever was not present or not measured. A third or fourth scan never contributed to the final diagnosis when the second one did not., Conclusions: [ 18 F]FDG-PET/CT contributed to the final diagnosis in 45.2% of patients, but never contributed when both inflammatory parameters and body temperature were normal. Repeating [ 18 F]FDG-PET/CT should only be done in patients with a non-contributory [ 18 F]FDG-PET/CT when new symptoms or signs appear, or when the first scan was made in absence of fever or elevated inflammatory parameters.

FDG-PET/CT has proven its clinical value and cost-effectiveness in diagnosing metastatic infections in patients with Gram-positive bacteremia. In identification of metastatic foci, FDG-PET/CT is useful as a screening method when localizing symptoms are absent because it provides whole-body coverage. FDG-PET/CT detects early metabolic activity rather than the late anatomical changes as visualized by computed tomography and magnetic resonance imaging. FDG-PET/CT allows more precise localization of infection within a shorter time span between injection and diagnosis as compared to conventional nuclear imaging. This review focuses on the clinical application of imaging of metastatic infectious diseases, with an emphasis on FDG-PET/CT putting it in perspective with other imaging modalities.