_____________________________________________________________________________________________________ *Corresponding author: E-mail: mayiork@med.uoa.gr, emmanouil.magiorkinis@gmail.com; Journal of Advances in Medicine and Medical Research 32(5): 71-82, 2020; Article no.JAMMR.55305 ISSN: 2456-8899 (Past name: British Journal of Medicine and Medical Research, Past ISSN: 2231-0614, NLM ID: 101570965) The Role of PET/CT in the Investigation of Fever of Unknown Origin Ioanna Kotsiri 1 , Charalampos Panotopoulos 2 and E. Magiorkinis 3* 1 Department of Internal Medicine, Asklipeion General Hospital, Voula, Greece. 2 Department of Clinical Cardiology, General Hospital of Kalamata, Kalamata, Greece. 3 Department of Laboratory Medicine, Sotiria General Hospital for Chest Diseases, Athens, Greece. Authors’ contributions This work was carried out in collaboration among all authors. Authors IK and EM designed the study, wrote the protocol, and wrote the first draft of the manuscript. Authors IK, EM and CP managed the analyses of the study. Authors CP and IK managed the literature searches. All authors read and approved the final manuscript. Article Information DOI:10.9734/JAMMR/2020/v32i530417 Editor(s): (1) Associate Prof. Maria Aparecida Visconti, Universidade de São Paulo, Brasil. Reviewers: (1) Dario Siniscalco, University of Campania, Italy. (2) Zhen Yuan, University of Macau, China. (3) Iman Fawzy Montasser, Ain Shams University, Egypt. Complete Peer review History: http://www.sdiarticle4.com/review-history/55305 Received 06 February 2020 Accepted 11 April 2020 Published 16 April 2020 ABSTRACT Aims: Fever of unknown origin (FUO) remains a diagnostic challenge for clinicians. The current diagnostic approach includes a detailed medical history, physical examination, laboratory tests and imaging techniques (chest X-ray, ultrasound, CT, MRI). 18F-FDG PET/CT (18fluoro-deoxyglucose PET/CT) is a non-invasive diagnostic imaging technique, which is widely used in oncology. The purpose of our narrative review was to summarize the knowledge for the diagnostic role of 18F-FDG PET/CT in the diagnostic approach of patients with FUO, as reported in the literature. Methodology: We undertook a search of literature published in PubMed until February 2019. Results: Various studies showed that 18F-FDG PET/CT could play an important role as a second- line explorative technique in the diagnosis of patients with FUO. 18F-FDG PET/CT presents high diagnostic accuracy in large vessel vasculitis, in orthopedic prosthetic infections, in chronic osteomyelitis and in prosthetic valve endocarditis. However, 18 -FDG/PET has some limitations such as the assessment of urine tract due to the excretion into the urine but also become of the high glucose metabolism in some organs such as the brain. Conclusions: Overall, PET/CT gains increasing interest in the diagnosis of FUO and should be considered by the clinicians in the exploration of those patients. Review Article