Molecular Imaging of Fever of Unknown Origin: An Update.

F-FDG PET/CT, Ga-citrate and white blood cell (WBC) scintigraphy are molecular imaging techniques currently used in the diagnostic workup of fever of unknown origin. However, it is unknown which technique fits which patient group best. A systematic literature search has been performed for original articles regarding the use of molecular imaging in fever of unknown origin. A total of 820 eligible studies were screened of which 63 articles evaluating 5094 patients met the inclusion criteria. F-FDG PET/CT provided good diagnostic accuracy (with a weighted mean sensitivity, specificity, positive predicting value, negative predictive value, accuracy and helpfulness of 84.4%, 61.8%, 80.7%, 67.8%, 76.3%, and 61.1%, respectively). Even within specific patient groups such as children, elderly, patients with connective tissue diseases, patients on renal replacement therapy, and HIV-infected patients, F-FDG PET/CT provided good diagnostic values. For Ga-citrate scintigraphy, the weighted mean sensitivity, specificity, positive predictive value, negative predictive value, and helpfulness were 42.2%, 80.3%, 82.4%, 41.9%, and 42.2%, respectively. WBC scintigraphy shows a weighted mean sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 73.5%, 86.3%, 79.1%, 82.4%, and 79.5%, respectively. However, compared to Ga-citrate and WBC scintigraphy, significantly more research has been performed using F-FDG PET/CT and F-FDG PET/CT has the advantage of relatively short procedural duration; it is therefore the preferred molecular diagnostic imaging technique. Ga-citrate and WBC scintigraphy can only be considered if F-FDG PET/CT is not available.