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Role of 18F FDG-PET-CT in Fever and Inflammation of Unknown Origin

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30 June 2025

Posted:

02 July 2025

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Abstract
Fever of unknown origin (FUO) and inflammation of unknown origin (IUO) remain complex diagnostic challenges due to their heterogeneous presentations and broad differential diagnoses. FUO was first described by Petersdorf and Beeson in 1961 and later redefined by Durack and Street, while IUO was introduced more recently by Vanderschueren et al. in 2009. Despite thorough investigations, a significant proportion of patients remain without a clear diagnosis, often resulting in prolonged hospital stays and increased healthcare costs. In recent years, [¹⁸F]FDG PET/CT has emerged as a valuable tool in the diagnostic workup of FUO and IUO, offering both metabolic and anatomical insights in a single scan. This review evaluates the diagnostic utility of [¹⁸F]FDG PET/CT, based on an analysis of 55 studies encompassing 6681 patients. The scan was found to be clinically helpful in 59% of cases, with diagnostic contributions from both true-positive and true-negative findings. Negative scans were frequently associated with spontaneous symptom resolution and fewer unnecessary interventions. However, differences in study design and definitions of diagnostic value make it difficult to compare results across studies. Overall, [¹⁸F]FDG PET/CT has proven to be a useful tool in the evaluation of FUO and IUO, and future research should focus on standardizing how its clinical benefit is measured and directly comparing its effectiveness with conventional imaging in well-designed prospective studies.
Keywords: 
infection
;  
inflammation
;  
FDG
;  
PET/CT
;  
FUO
;  
IUO
;  
fever of unknown origin
;  
inflammation of unknown origin
Subject: 
Medicine and Pharmacology  -   Other

1. Introduction

Fever of unknown origin (FUO) and inflammation of unknown origin (IUO) present significant diagnostic challenges in clinical practice.
FUO was first described by Drs. Petersdorf and Dr. Beesom in 1961 [1]; since then, the definition has undergone several revisions, with the latest widely accepted version proposed by Durack and Street in 1991, characterizing it as a fever of 101°F (38.3°C) or higher on more than 3 occasions, without a diagnosis despite 3 days of relevant inpatient workup or 3 outpatient visits [2].
IUO, on the other hand, has a more recent history, first described by Vanderschueren et al. in 2009, who outlined it as an illness lasting more than three weeks, during which the body temperature is ≤38.3°C on several occasions, the inflammatory markers are elevated (C-reactive protein (CRP) ≥ 30 mg/L or increase erythrocyte sedimentation rate), and for which no diagnosis could be established, despite minimal investigation, during at least three outpatient visits or 3 days of hospital investigation [3].
Despite thorough initial evaluations, many patients still remain undiagnosed, leading to prolonged workups, increased healthcare costs, and compromised outcomes.
With a wide range of possible differential diagnoses, spanning from infectious to non-infectious diseases, from malignancies to miscellaneous disease, a systematic, multidisciplinary approach is essential to identify active disease early and to guide the right therapy.
In recent years, [¹⁸F]FDG PET/CT has become a key tool in the diagnostic workup for FUO and IUO. Its use in everyday clinical settings—either as a first- or second-line modality—is getting increasingly common, particularly when conventional imaging fails to identify a cause. As set forth by the European Association of Nuclear Medicine (EANM), this imaging technique combines metabolic and anatomical information in a single scan, allowing for precise localization and characterization of pathological FDG uptake [4]. Moreover, recently published Delphi-generated consensus-based recommendations on FUO/IUO listed [¹⁸F]FDG PET/CT in the strong consensus agreement as “an important diagnostic test (to perform) after a patient fulfills the FUO criteria with minimal diagnostic tests” and that “clinicians should consider earlier use of [¹⁸F]FDG PET/CT, after plain radiography or CT, particularly in the absence of potential diagnostic clues” [5]. Recent studies, including work by Buchrits et al. [6], report a diagnostic contribution in over 75% of cases, highlighting its ability to both detect underlying disease and exclude focal pathology. As nuclear medicine advances, [¹⁸F]FDG PET/CT is expected to further enhance diagnostic accuracy. Its integration into the diagnostic pathway helps optimize outcomes, reduce unnecessary interventions, and improve the overall management of patients with FUO and IUO.
This review aims to assess the role of [¹⁸F]FDG PET/CT in the evaluation of FUO and IUO, as supported by current literature.

2. Methodology

A comprehensive search of existing literature was performed on PubMed and Cochrane library from 2001 up to May 2025, using the following search terms: (PET OR FDG OR fluorodeoxyglucose) AND (fever OR FUO OR PUO OR pyrexia OR inflammation OR IUO). We included prospective, retrospective and ambispective studies that examined the contribution of [¹⁸F]FDG PET/CT to the investigation of “fever of unknown origin” as defined by Durack [2] and of “inflammation of unknown origin” as defined by Vanderschueren” [3]. The complete PubMed search string is presented in Table 1 [7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61].
We excluded studies that assessed the contribution of [¹⁸F]FDG PET alone without the component of CT and studies that assessed [¹⁸F]FDG PET associated with MRI.
The primary goal was to assess the clinical helpfulness of [¹⁸F]FDG PET/CT to the final diagnosis of fever of unknown origin or inflammation of unknown origin, which was defined, depending on the study, as True Positive or as True Positive summed to the True Negative (as reported in Table 1). We also reported, when available or possible to extract from known data, sensitivity and specificity, positive predictive value and negative predictive value of [¹⁸F]FDG PET/CT, as shown in Table 2 [7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61].
Table 1. Characteristics of included studies.
Table 1. Characteristics of included studies.
First author Year Patients n. Population Study type Final diagnosis
Jaruskova[7] 2006 94 FUO R NR
Bleeker-Rovers[8] 2006 70 FUO P 0.50
Keidar[9] 2008 48 FUO P 0.60
Balink[10] 2009 68 FUO R 0.65
Federici[11] 2010 14 FUO/IUO R 0.71
Ferda[12] 2010 48 FUO R 0.92
Kei[13] 2010 12 FUO R 0.58
Ergül[14] 2011 24 FUO R 0.54
Kubota[15] 2011 81 FUO R 0.75
Pelosi[16] 2011 24 FUO R 0.71
Sheng[17] 2011 48 FUO R 0.75
Rosenbaum[18] 2011 24 FUO R 1.00
Becerra Nakayo[19] 2012 20 FUO R NR
Crouzet[20] 2012 79 FUO R 0.77
Kim[21] 2012 48 FUO R 0.85
Pedersen[22] 2012 22 FUO R 0.60
Manohar[23] 2013 103 FUO R 0.67
Balink[24] 2014 140 IUO R 0.74
Buch-Olsen[25] 2014 57 FUO R 0.91
Tokmak[26] 2014 25 FUO R 0.92
Balink[27] 2015 498 FUO/IUO R 0.66
Gafter-Gvili[28] 2015 112 FUO R 0.74
Singh[29] 2015 47 FUO P 0.53
Bouter[30] 2016 72 FUO/IUO R 0.83
Pereira[31] 2016 76 FUO R 0.93
Hung[32] 2017 58 FUO P 0.79
Abdelrahman[33] 2018 27 FUO P 0.92
Garcia-Vicente[34] 2018 67 FUO R 0.88
Schönau[35] 2018 240 FUO/IUO P 0.79
Wang[36] 2019 376 FUO/IUO R 0.91
Wang[37] 2020 147 FUO/IUO P 0.88
Georga[38] 2020 50 FUO R 0.78
Zhu[39] 2020 89 FUO/IUO R 0.74
Kubota[40] 2021 128 FUO P 0.72
Letertre[41] 2021 44 FUO R 0.70
MuldersManders[42] 2021 104 FUO/IUO R 0.65
Bilici Salman[43] 2021 97 IUO R 0.90
Mahajna[44] 2021 128 FUO R 0.74
Das[45] 2021 43 FUO R 0.74
Yadav[46] 2021 51 FUO P 0.88
Buchritis[47] 2021 303 FUO R 0.72
Chen[48] 2022 524 FUO P 0.91
Chen[49] 2022 326 FUO/IUO R 0.91
Holubar[50] 2022 317 IUO R 0.72
Ogut[51] 2022 58 FUO/IUO R 0.90
Ly[52] 2022 103 FUO/IUO P 0.56
Weitzer[53] 2022 300 FUO/IUO R 0.84
Becker KK[54] 2024 77 FUO/IUO R 1.00
Fathala[55] 2024 105 FUO R 1.00
Khan[56] 2024 573 FUO A 0.38
Liu[57] 2024 40 FUO R 1.00
Kobayashi[58] 2024 45 FUO/IUO R 0.71
Koreli[59] 2025 30 FUO/IUO R 0.50
Yu[60] 2025 284 FUO R 0.69
Greuez[61] 2025 93 FUO/IUO R 0.59
*FUO: fever of unknown origin; IUO: inflammation of unknown origin; R: retrospective; P: prospective; A: ambispective; NR: not reported.
Table 2. FDG PET-CT contributory results in examined studies.
Table 2. FDG PET-CT contributory results in examined studies.
First author Clinical Helpfulness Sensitivity Specificity PPV NPV
Jaruskova[7] 0.36 NR NR NR NR
Bleeker-Rovers[8] 0.33 (TP) 0.88 0.77 0.70 0.92
Keidar[9] 0.90 (TP+TN) 1.00 0.81 0.81 1.00
Balink[10] 0.56 (TP) 1.00 0.90 0.93 1.00
Federici[11] 0.50 (TP) 0.70 0.75 0.88 0.5
Ferda[12] 0.77 0.97 0.75 NR NR
Kei[13] 0.42 (TP) NR NR NR NR
Ergül[14] 0.63 0.92 0.45 0.63 1.0
Kubota[15] 0.54 0.81 0.75 NR NR
Pelosi[16] 0.87 (TP+TN) 0.50 0.50 0.85 0.85
Sheng[17] 0.67 0.89 0.33 0.80 0.50
Rosenbaum[18] 1.00 (TP+TN) NR NR NR NR
Becerra Nakayo[19] 0.55 (TP) 0.78 0.83 0.92 0.62
Crouzet[20] 0.19 0.98 0.87 NR NR
Kim[21] 0.56 0.92 0.23 NR NR
Pedersen[22] 0.83 0.67 0.71 0.83 0.50
Manohar[23] 0.60 0.90 0.97 0.98 0.83
Balink[24] 0.51 0.94 0.83 0.93 0.77
Buch-Olsen[25] 0.75 (TP+TN) NR NR NR NR
Tokmak[26] 0.60 (TP) 0.94 0.80 NR NR
Balink[27] 0.59 (TP) 0.89 0.89 0.94 0.80
Gafter-Gvili[28] 0.66 0.72 0.58 0.74 0.54
Singh[29] 0.38 (TP) NR NR NR NR
Bouter[30] 0.65 (TP) 0.81 0.86 NR NR
Pereira[31] 0.61 0.77 0.31 0.61 0.50
Hung[32] 0.72 0.79 0.56 0.83 0.50
Abdelrahman[33] 0.85 (TP) 0.95 0.67 0.96 0.67
Garcia-Vicente[34] 0.52 0.84 0.31 NR NR
Schönau[35] 0.57 (TP) 0.91 0.22 0.65 0.62
Wang[36] 0.90 NR NR NR NR
Wang[37] 0.58 0.88 0.15 0.59 0.47
Georga[38] 0.72 (TP) 0.94 0.50 0.86 0.75
Zhu[39] 0.74 (TP+TN) 0.84 0.26 NR NR
Kubota[40] 0.33 (TP) 0.45 0.40 0.67 NR
Letertre[41] 0.44 0.85 0.37 0.58 0.70
MuldersManders[42] 0.45 NR NR NR NR
Bilici Salman[43] 0.61 (TP) 0.67 1.00 1.00 0.26
Mahajna[44] 0.48 (TP) 0.70 0.37 0.70 0.34
Das[45] 0.91 (TP+TN) 0.77 0.33 0.83 0.25
Yadav[46] 0.63 NR NR NR NR
Buchritis[47] 0.26 0.89 0.81 NR NR
Chen[48] 0.91 NR NR NR NR
Chen[49] 0.96 NR NR NR NR
Holubar[50] 0.75 (TP+TN) 0.84 0.62 0.77 0.72
Ogut[51] 0.72 (TP+TN) 0.88 0,37 0.79 0,55
Ly[52] 0.19 (TP) 0.36 0.81 NR NR
Weitzer[53] 0.54 (TP) 0.80 0.90 NR NR
Becker KK[54] 0.61 (TP+TN) NR NR NR NR
Fathala[55] 0.72 (TP+TN) 0.72 0.29 0.68 0.33
Khan[56] 0.16 (TP) NR NR NR NR
Liu[57] 0.98 0.93 0.62 0.83 0.80
Kobayashi[58] 0.64 0.91 0.38 0.78 0.62
Koreli[59] 0.50 (TP) 1.00 0.33 0.60 1.00
Yu[60] 0.48 0.79 0.61 0.76 0.63
Greuez[61] 0.31 NR NR NR NR
* PPV: positive predictive value; NPV: negative predictive value; TP: true positive; TN: true negative; NR: not reported.

3. Results

The literature search yielded 605 potentially pertinent publications. Among them, 549 articles were found to be unrelated to the subject or were the wrong study type. Ultimately, we included 55 studies, with a total of 6681 patients. We listed in Table 1 the general features of each study: this review included mostly retrospective studies (78%), a few prospective studies (20%) and only 1 ambispective study. Of these, 36 studies focused on patients presenting with fever of unknown origin, 3 studies examined patients with inflammation of unknown origin, and 16 studies comprised both these populations. Table 2 describes the main findings of the considered studies. Fifty-three studies out of the total fifty-five analysed reported the number of patients who received a final diagnosis: out of 6567 patients for whom the study reported a final diagnosis, the underlying cause of FUO or IUO was identified in 4917 of them (75%); in most of the remaining cases fever resolved spontaneously.
A precise definition for clinical helpfulness of [¹⁸F]FDG PET/CT was not always reported in the analysed studies: it was specified, as a matter of fact, in only twenty-nine studies (53%). Among these twenty-nine studies, in nineteen works (65%) the diagnostic contribution of [¹⁸F]FDG PET/CT scan was delineated as impactful exclusively when abnormal uptake was localized to a specific organ or tissue, and subsequent specific conventional diagnostic modalities confirmed a definitive diagnosis (true positive scans, TP). Ten studies defined [¹⁸F]FDG PET/CT as a “valuable” test when the imaging either provided information that directly led to the final diagnosis (TP) or when it showed no focal FDG uptake (true negative, TN), consistent with the absence of disease in the final diagnosis.
Overall, [¹⁸F]FDG PET/CT was found to be contributory to the diagnostic workup in 59% of all examined cases (it was considered as clinically helpful in a total of 3919 patients over the 6681 observed).

3. Discussion

The diagnostic evaluation of patients with FUO or IUO presents significant methodological challenges due to the heterogeneity of potential etiologies, the absence of universally accepted reference standards, and the considerable proportion of patients who remain without a definitive diagnosis. Timely and accurate diagnosis significantly influences the therapeutic approach in patients with FUO. Early identification of the underlying etiology can lead to the initiation of appropriate treatment, adjustment of ongoing therapies, or a complete change in the therapeutic regimen. Moreover, a precise diagnosis can guide targeted diagnostic interventions, both invasive and noninvasive—such as biopsy, drainage procedures, serological testing, and cultures of blood, urine, or tissues—with potential implications for cost-effectiveness and clinical efficiency [10]. [18F]FDG PET/CT plays a crucial role in the diagnostic work-up of FUO by directing the clinician toward the most suitable and accessible biopsy site, thereby facilitating histological confirmation of the underlying disease. Additionally, [18F]FDG PET/CT contributes indirectly by helping to rule out numerous potential causes, effectively narrowing the differential diagnosis [38].
Most existing studies only take in consideration [¹⁸F]FDG PET/CT as a useful tool when it directly correlates to the final diagnosis (true positive), while true negative studies are often underreported, despite their relevance in excluding significant pathology, predicting spontaneous clinical resolution, and potentially reducing unnecessary diagnostic procedures [9,16,24,34,40,62]. Moreover, negative PET/CT scans have been significantly associated with spontaneous remission [63]. While true-positive (TP) findings are essential for establishing a definitive diagnosis, true-negative (TN) results are equally valuable in excluding potential causes. In the context of FUO and IUO, previous studies have reported that the absence of pathological [¹⁸F]FDG PET/CT uptake on PET/CT is frequently associated with spontaneous resolution [28,62]. This finding has important clinical implications, as supported by Takeuchi et al.’s recent meta-analysis [63], demonstrating that patients with negative PET-CT results are significantly more likely to experience spontaneous resolution of symptoms compared to those with positive findings. These results emphasize the utility of a negative PET-CT not only as a diagnostic exclusion tool but also as a means to guide clinical management. Specifically, it may help avoid unnecessary invasive diagnostic procedures and limit the use of potentially inappropriate treatments, such as empirical antibiotic therapy [64].
However, a substantial proportion of FUO/IUO patients—ranging from 7% to 62% in the studies taken into consideration in our literature search—remained undiagnosed after [¹⁸F]FDG PET/CT. In light of these limitations, the more general concept of “clinical helpfulness”—defined as the proportion of scans that inform subsequent clinical decision-making—offers a more comprehensive assessment of [¹⁸F]FDG PET/CT’s value in this population with respect to more classical parameters like specificity and sensitivity [65,66,67]. The analysed studies reported an overall clinical helpfulness ranging from 16% to 100% (with a mean value of 60%), with higher values observed when both true-positive and true-negative results were considered: indeed, studies that counted PET/CT scans as helpful when they showed either true positive or true negative results reported an overall usefulness of 61% to 100%. In contrast, studies that only considered true positive results showed a usefulness ranging from 16% to 85%.
A sizable prospective study [48] by Chen’s group, that examined 524 patients over the course of 5 years, found [¹⁸F]FDG PET/CT to be positive in 91% of patients (477/524; diffuse or focal high uptake of FDG in various organs and tissues), and the model demonstrated excellent discrimination for infection (AUC = 0.88), malignancy (AUC = 0.93), and NIID (AUC = 0.95). Notably, several studies included in this analysis only unacknowledged focal uptake as impactful, while excluding other “nonspecific” uptake from consideration (such as diffuse uptake in the spleen, bone marrow, or symmetrical lymphadenopathy) [9,14,28,35,36].
In conclusion, while the accuracy of [¹⁸F]FDG PET/CT in evaluating FUO/IUO can be affected by a range of factors—including patient complexity, definitions of FUO/IUO, timing, and variability in reference standards—most studies agree that it often provides useful information for clinical decision-making. A positive scan can be key to making a diagnosis, and sometimes it's even essential. Positive scans frequently contribute to, and occasionally are indispensable for, establishing a diagnosis. Conversely, negative scans can rule out focal disease and are associated with a high likelihood of spontaneous remission, thus serving as valuable prognostic tools. Moving forward, well-designed prospective studies are needed to further refine its diagnostic role in FUO/IUO workup.

4. Conclusions and future Directions

FUO and IUO continue to present significant diagnostic challenges due to the heterogeneity of clinical presentations, a wide range of potential underlying etiologies, and the lack of a standardized diagnostic approach. The existing literature mirrors this complexity, making it challenging to compare or combine study results. [¹⁸F]FDG PET/CT has shown a valuable role in this setting, with positive scans often helping to establish a diagnosis, while negative scans may also be clinically relevant by excluding localized disease and suggesting a better prognosis. For future research, the contribution of PET/CT should be defined as the sum of true positives and true negatives to improve accuracy and consistency. Additional studies, especially randomized controlled trials comparing PET/CT to conventional CT, are needed to determine the most effective first-line imaging modality in the evaluation of FUO/IUO.

Author Contributions

Conceptualization, methodology: Lucia Leccisotti; formal analysis, investigation, data curation, writing—original draft preparation, Elena Romano Gargarella; writing—review and editing, Lucia Leccisotti, Andrea Guarneri, Vocaturo Flaminia; supervision, Lucia Leccisotti, Andrea Guarneri. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Conflicts of Interest

The authors declare no conflicts of interest.

Abbreviations

The following abbreviations are used in this manuscript:
FUO Fever of unknown origin
IUO Inflammation of unknown origin
FDG Fluorodeoxyglucose
PET-CT Positron emission tomography/computed tomography
PPV positive predictive value
NPV negative predictive value
NR not reported
TP True Positive
TN True Negative
R Retrospective
P Prospective
A Ambispective

References

  1. Petersdorf, R. G.; Beeson, P. B. Fever of unexplained origin: report on 100 cases. Medicine 1961, 40, 1–30. [Google Scholar] [CrossRef] [PubMed]
  2. Durack, D. T.; Street, A. C. Fever of unknown origin--reexamined and redefined. Current clinical topics in infectious diseases 1991, 11, 35–51. [Google Scholar]
  3. Vanderschueren, S.; Del Biondo, E.; Ruttens, D.; Van Boxelaer, I.; Wauters, E.; Knockaert, D.D. Inflammation of unknown origin versus fever of unknown origin: two of a kind. European journal of internal medicine 2009, 20, 415–418. [Google Scholar] [CrossRef]
  4. Hess, S.; Noriega-Álvarez, E.; Leccisotti, L.; Treglia, G.; Albano, D.; Roivainen, A.; Glaudemans, A.W.J. M.; Gheysens, O. 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, 51, 2597–2613. [Google Scholar] [CrossRef] [PubMed]
  5. Wright, W. F.; Stelmash, L.; Betrains, A.; Mulders-Manders, C. M.; Rovers, C. P.; Vanderschueren, S.; Auwaerter, P. G. International Fever and Inflammation of Unknown Origin Research Working Group Recommendations for Updating Fever and Inflammation of Unknown Origin From a Modified Delphi Consensus Panel. Open forum infectious diseases 2024, 11, ofae298. [Google Scholar] [CrossRef] [PubMed]
  6. Buchrits, S.; McNeil, R.; Avni, T.; Fredman, D.; Guz, D.; Gafter-Gvili, A. The Contribution of 18F FDG PET-CT for the Investigation of Fever of Unknown Origin and Inflammation of Unknown Origin. The American journal of medicine 2024, 137, 629–639. [Google Scholar] [CrossRef]
  7. Jaruskova, M.; Belohlavek, O. Role of FDG-PET and PET/CT in the diagnosis of prolonged febrile states. Eur J Nucl Med Mol Imaging. 2006, 33, 913–918. [Google Scholar] [CrossRef]
  8. Bleeker-Rovers, C.P.; Vos, F.J.; de Kleijn, E.; Mudde, A.H.; Dofferhoff, T.S.M.; Richter, C.; et al. A prospective multicenter study on fever of unknown origin: the yield of a structured diagnostic protocol. Medicine. 2007, 86, 26–38. [Google Scholar] [CrossRef]
  9. Keidar, Z.; Gurman-Balbir, A.; Gaitini, D.; Israel, O. Fever of unknown origin: the role of 18F-FDG PET/CT. Journal of nuclear medicine: official publication. Soc Nuclear Med. 2008, 49, 1980–1985. [Google Scholar] [CrossRef]
  10. Balink, H.; Collins, J.; Bruyn, G.A.; Gemmel, F. F-18 FDG PET/CT in the diagnosis of fever of unknown origin. Clin Nucl Med. 2009, 34, 862–868. [Google Scholar] [CrossRef]
  11. Federici, L.; Blondet, C.; Imperiale, A.; Sibilia, J.; Pasquali, J.L.; Pflumio, F.; et al. Value of (18)F-FDG-PET/CT in patients with fever of unknown origin and unexplained prolonged inflammatory syndrome: a single centre analysis experience. Int J Clin Pract. 2010, 64, 55–60. [Google Scholar] [CrossRef]
  12. Ferda, J.; Ferdova, E.; Zahlava, J.; Matejovic, M.; Kreuzberg, B. Fever of unknown origin: a value of (18)F-FDG-PET/CT with integrated full diagnostic isotropic CT imaging. Eur J Radiol. 2010, 73, 518–525. [Google Scholar] [CrossRef]
  13. Kei, P.L.; Kok, T.Y.; Padhy, A.K.; Ng, D.C.; Goh, A.S. [18F] FDG PET/CT in patients with fever of unknown origin: a local experience. Nucl Med Commun. 2010, 31, 788–792. [Google Scholar] [CrossRef] [PubMed]
  14. Ergul, N.; Halac, M.; Cermik, T.F.; Ozaras, R.; Sager, S.; Onsel, C.; et al. The diagnostic role of FDG PET/CT in patients with fever of unknown origin. Mol Imaging Radionucl Therapy. 2011, 20, 19–25. [Google Scholar] [CrossRef]
  15. Kubota, K.; Nakamoto, Y.; Tamaki, N.; Kanegae, K.; Fukuda, H.; Kaneda, T.; et al. FDG-PET for the diagnosis of fever of unknown origin: a Japanese multi-center study. Ann Nucl Med. 2011, 25, 355–364. [Google Scholar] [CrossRef]
  16. Pelosi, E.; Skanjeti, A.; Penna, D.; Arena, V. Role of integrated PET/CT with [(1)(8)F]-FDG in the management of patients with fever of unknown origin: a single-centre experience. Radiol Med. 2011, 116, 809–820. [Google Scholar] [CrossRef] [PubMed]
  17. Sheng, J.F.; Sheng, Z.K.; Shen, X.M.; Bi, S.; Li, J.J.; Sheng, G.P.; et al. Diagnostic value of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography in patients with fever of unknown origin. Eur J Intern Med. 2011, 22, 112–116. [Google Scholar] [CrossRef] [PubMed]
  18. Rosenbaum, J.; Basu, S.; Beckerman, S.; Werner, T.; Torigian, D. A.; Alavi, A. Evaluation of diagnostic performance of 18F-FDG-PET compared to CT in detecting potential causes of fever of unknown origin in an academic centre. Hellenic journal of nuclear medicine 2011, 14, 255–259. [Google Scholar]
  19. Becerra Nakayo, E.M.; Garcia Vicente, A.M.; Soriano Castrejon, A.M.; Mendoza Narvaez, J.A.; Talavera Rubio, M.P.; Poblete Garcia, V.M.; et al. [Analysis of cost-effectiveness in the diagnosis of fever of unknown origin and the role of (18)F-FDG PET-CT: a proposal of diagnostic algorithm]. Revista Esp De Med Nuclear e Imagen Mol. 2012, 31, 178–186. [Google Scholar] [CrossRef]
  20. Crouzet, J.; Boudousq, V.; Lechiche, C.; Pouget, J.P.; Kotzki, P.O.; Collombier, L.; et al. Place of (18)F-FDG-PET with computed tomography in the diagnostic algorithm of patients with fever of unknown origin. Eur J Clin Microbiol Infect Diseases: Official Publication Eur Soc Clin Microbiol. 2012, 31, 1727–1733. [Google Scholar] [CrossRef]
  21. Kim, Y.J.; Kim, S.I.; Hong, K.W.; Kang, M.W. Diagnostic value of 18F-FDG PET/CT in patients with fever of unknown origin. Intern Med J. 2012, 42, 834–837. [Google Scholar] [CrossRef] [PubMed]
  22. Pedersen, T.I.; Roed, C.; Knudsen, L.S.; Loft, A.; Skinhoj, P.; Nielsen, S.D. Fever of unknown origin: a retrospective study of 52 cases with evaluation of the diagnostic utility of FDG-PET/CT. Scand J Infect Dis. 2012, 44, 18–23. [Google Scholar] [CrossRef]
  23. Manohar, K.; Mittal, B.R.; Jain, S.; Sharma, A.; Kalra, N.; Bhattacharya, A.; et al. F-18 FDG-PET/CT in evaluation of patients with fever of unknown origin. Japanese J Radiol. 2013, 31, 320–327. [Google Scholar] [CrossRef] [PubMed]
  24. Balink, H.; Bennink, R.J.; Veeger, N.J.; van Eck-Smit, B.L.; Verberne, H.J. Diagnostic utility of (18)F-FDG PET/CT in inflammation of unknown origin. Clin Nucl Med. 2014, 39, 419–425. [Google Scholar] [CrossRef]
  25. Buch-Olsen, K. M.; Andersen, R. V.; Hess, S.; Braad, P. E.; Schifter, S. 18F-FDG-PET/CT in fever of unknown origin: clinical value. Nuclear medicine communications 2014, 35, 955–960. [Google Scholar] [CrossRef]
  26. Tokmak, H.; Ergonul, O.; Demirkol, O.; Cetiner, M.; Ferhanoglu, B. Diagnostic contribution of (18)F-FDG-PET/CT in fever of unknown origin. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases 2014, 19, 53–58. [Google Scholar] [CrossRef]
  27. Balink, H.; Veeger, N.J.; Bennink, R.J.; Slart, R.H.; Holleman, F.; van Eck-Smit, B.L.; et al. The predictive value of C-reactive protein and erythrocyte sedimentation rate for 18F-FDG PET/CT outcome in patients with fever and inflammation of unknown origin. Nucl Med Commun. 2015, 36, 604–609. [Google Scholar] [CrossRef] [PubMed]
  28. Gafter-Gvili, A.; Raibman, S.; Grossman, A.; Avni, T.; Paul, M.; Leibovici, L.; et al. [18F]FDG-PET/CT for the diagnosis of patients with fever of unknown origin. QJM: Monthly J Association Physicians. 2015, 108, 289–298. [Google Scholar] [CrossRef]
  29. Singh, N.; Kumar, R.; Malhotra, A.; Bhalla, A.S.; Kumar, U.; Sood, R. Diagnostic utility of fluorodeoxyglucose positron emission tomography/computed tomography in pyrexia of unknown origin. Indian J Nuclear Medicine: IJNM: Official J Soc Nuclear Med India. 2015, 30, 204–212. [Google Scholar] [CrossRef]
  30. Bouter, C.; Braune, I.; Meller, B.; Sahlmann, C.; Ritter, C.; Meller, J. (18)F-FDG-PET/CT in unexplained elevated inflammatory markers. Join Entities Nuklearmedizin. 2016, 55, 242–249. [Google Scholar] [CrossRef]
  31. Pereira, A.M.; Husmann, L.; Sah, B.R.; Battegay, E.; Franzen, D. Determinants of diagnostic performance of 18F-FDG PET/CT in patients with fever of unknown origin. Nucl Med Commun. 2016, 37, 57–65. [Google Scholar] [CrossRef] [PubMed]
  32. Hung, B.T.; Wang, P.W.; Su, Y.J.; Huang, W.C.; Chang, Y.H.; Huang, S.H.; et al. The efficacy of (18)F-FDG PET/CT and (67)Ga SPECT/CT in diagnosing fever of unknown origin. Int J Infect Diseases: IJID: Official Publication Int Soc Infect Dis. 2017, 62, 10–17. [Google Scholar] [CrossRef] [PubMed]
  33. Abdelrahman, S.F.E.; El-nasr, S.D.; Gadalla, S.I.S.E.H. Value of 18-F-FDG PET/CT in assessment of patients with fever of unknown origin. Egypt J Radiol Nuclear Med. 2018, 49, 461–466. [Google Scholar] [CrossRef]
  34. Garcia-Vicente, A.M.; Tello-Galan, M.J.; Amo-Salas, M.; Ros-Izquierdo, J.; Jimenez-Londono, G.A.; La Rosa Salas, B.; et al. Do clinical and laboratory variables have any impact on the diagnostic performance of 18F-FDG PET/CT in patients with fever of unknown origin? Ann Nucl Med. 2018, 32, 123–131. [Google Scholar] [CrossRef]
  35. Schonau, V.; Vogel, K.; Englbrecht, M.; Wacker, J.; Schmidt, D.; Manger, B.; et al. The value of (18)F-FDG-PET/CT in identifying the cause of fever of unknown origin (FUO) and inflammation of unknown origin (IUO): data from a prospective study. Ann Rheum Dis. 2018, 77, 70–77. [Google Scholar] [CrossRef]
  36. Wang, Q.; Li, Y.M.; Li, Y.; Hua, F.C.; Wang, Q.S.; Zhang, X.L.; et al. 18)F-FDGPET/CT in fever of unknown origin and inflammation of unknown origin: a Chinese multi-center study. Eur J Nucl Med Mol Imaging. 2019, 46, 159–165. [Google Scholar] [CrossRef] [PubMed]
  37. Wang, W.X.; Cheng, Z.T.; Zhu, J.L.; Xing, M.Y.; Zheng, C.F.; Wang, S.J.; et al. Combined clinical parameters improve the diagnostic efficacy of (18)F-FDG PET/CT in patients with fever of unknown origin (FUO) and inflammation of unknown origin (IUO): a prospective study in China. Int J Infect Diseases: IJID: Official Publication Int Soc Infect Dis. 2020, 93, 77–83. [Google Scholar] [CrossRef]
  38. Georga, S.; Exadaktylou, P.; Petrou, I.; Katsampoukas, D.; Mpalaris, V.; Moralidis, E.I.; et al. Diagnostic value of (18)F-FDG-PET/CT in patients with FUO. J Clin Med. 2020, 9. [Google Scholar]
  39. Zhu, W.; Cao, W.; Zheng, X.; Li, X.; Li, Y.; Chen, B.; et al. The diagnostic value of (18)F-FDG PET/CT in identifying the causes of fever of unknown origin. Clin Med. 2020, 20, 449–453. [Google Scholar] [CrossRef]
  40. Kubota, K.; Tanaka, N.; Miyata, Y.; Ohtsu, H.; Nakahara, T.; Sakamoto, S.; et al. Comparison of (18)F-FDG PET/CT and (67)Ga-SPECT for the diagnosis of fever of unknown origin: a multicenter prospective study in Japan. Ann Nucl Med. 2021, 35, 31–46. [Google Scholar] [CrossRef]
  41. Letertre, S.; Fesler, P.; Zerkowski, L.; Picot, M.C.; Ribstein, J.; Guilpain, P.; et al. Place of the (18)F-FDG-PET/CT in the diagnostic workup in patients with classical fever of unknown origin (FUO). J Clin Med. 2021, 10. [Google Scholar]
  42. Mulders-Manders, C.M.; Kouijzer, I.J.; Janssen, M.J.; Oyen, W.J.; Simon, A.; Bleeker-Rovers, C.P. Optimal use of [18F]FDG-PET/CT in patients with fever or inflammation of unknown origin. The quarterly journal of nuclear medicine and molecular imaging: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR) [and] Sect So. 2021, 65, 51–58. [Google Scholar] [CrossRef]
  43. Bilici Salman, R.; Gülbahar Ateş, S.; Satiş, H.; Tufan, A.; Akdemir, Ü.; Yapar, D.; et al. Diagnostic role of 18F-Fluorodeoxyglucose Positron Emission Tomography for the evaluation of patients with inflammation of unknown origin. J Clin Rheumatology: Practical Rep Rheumatic Musculoskelet Dis. 2021, 27, 219–225. [Google Scholar] [CrossRef]
  44. Mahajna, H.; Vaknin, K.; Ben Shimol, J.; Watad, A.; Abu-Much, A.; Mahroum Net, a.l. The utility of 18FDG-PET/CT in diagnosing fever of unknown origin: the experience of a large tertiary medical center. Int J Environ Res Public Health. 2021, 18. [Google Scholar] [CrossRef] [PubMed]
  45. Das, S.; Sathyendra, S.; Hephzibah, J.; Karuppusami, R.; Gunasekaran, K.; Shanthly, N.; Miraclin, A.; Iyadurai, R. Utility of positron emission tomography-computed tomography in the evaluation of fever of unknown origin in a resource-limited tropical nation. World journal of nuclear medicine 2021, 20, 237–246. [Google Scholar] [CrossRef]
  46. Yadav, B.K.; Pannu, A.K.; Kumar, R.; Rohilla, M.; Kumari, S. Fever of unknown origin in older adults: a prospective observational study from North India. J Assoc Physicians India. 2021, 69, 11–12. [Google Scholar]
  47. Buchrits, S.; Gafter-Gvili, A.; Eynath, Y.; Bernstine, H.; Guz, D.; Avni, T. The yield of F(18) FDG PET-CT for the investigation of fever of unknown origin, compared with diagnostic CT. Eur J Intern Med. 2021, 93, 50–56. [Google Scholar] [CrossRef]
  48. Chen, J.; Xing, M.; Xu, D.; Xie, N.; Zhang, W.; Ruan, Q.; et al. Diagnostic models for fever of unknown origin based on (18)F-FDG PET/CT: a prospective study in China. EJNMMI Res. 2022, 12, 69. [Google Scholar] [CrossRef] [PubMed]
  49. Chen, J.C.; Wang, Q.; Li, Y.; Zhao, Y.Y.; Gao, P.; Qiu, L.H.; et al. Current situation and cost-effectiveness of (18)F-FDG PET/CT for the diagnosis of fever of unknown origin and inflammation of unknown origin: a single-center, large-sample study from China. Eur J Radiol. 2022, 148, 110184. [Google Scholar] [CrossRef]
  50. Holubar, J.; Broner, J.; Arnaud, E.; Hallé, O.; Mura, T.; Chambert, B.; et al. Diagnostic performance of (18) F-FDG-PET/CT in inflammation of unknown origin: a clinical series of 317 patients. J Intern Med. 2022, 291, 856–863. [Google Scholar] [CrossRef]
  51. Öğüt, T.S.; Erbasan, F.; Terzioğlu, M.E.; Tazegul, G.; Yazısız, V. The Diagnostic Value of Fluoro-18 fluorodeoxyglucose (F-18 FDG) PET/CT in fever or inflammation of unknown origin: a retrospective study at a Rheumatology Clinic. Cureus. 2022, 14, e24192. [Google Scholar] [CrossRef] [PubMed]
  52. Ly, K.H.; Costedoat-Chalumeau, N.; Liozon, E.; Dumonteil, S.; Ducroix, J.P.; Sailler, L.; et al. 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. J Clin Med. 2022, 11. [Google Scholar] [CrossRef] [PubMed]
  53. Weitzer, F.; Nazerani Hooshmand, T.; Pernthaler, B.; Sorantin, E.; Aigner, R.M. Diagnostic value of F-18 FDG PET/CT in fever or inflammation of unknown origin in a large single-center retrospective study. Sci Rep. 2022, 12, 1883. [Google Scholar] [CrossRef]
  54. Becker, K. K.; Søholm, J.; Hess, S. The Diagnostic Yield of [18F]FDG-PET/CT in a Heterogeneous In-Patient Population with Suspected Infection or Inflammation Is Comparable to Findings in Patients with Classic Fever of Unknown Origin. Diagnostics (Basel, Switzerland) 2024, 14, 1420. [Google Scholar] [CrossRef]
  55. Fathala, A.; Benkuddah, R.; Almuhaideb, A. Performance and value of 18F-FDG PET/CT in patients with fever of unknown origin. Biomedical reports 2024, 21, 169. [Google Scholar] [CrossRef]
  56. Khan, D.; Phulia, A.; Kumar, S.; Sarswat, S.; Kv, S.; Sagar, S. Role of 18 F-FDG PET/CT for providing a targeted approach for etiology of PUO. Nuclear medicine communications 2024, 45, 702–709. [Google Scholar] [CrossRef]
  57. Liu, B.; Ma, R.; Shum, E.; Hormiz, M.; Lee, S. T.; Poon, A. M. T.; Scott, A. M. FDG-PET/CT for investigation of pyrexia of unknown origin: a cost of illness analysis. European journal of nuclear medicine and molecular imaging 2024, 51, 1287–1296. [Google Scholar] [CrossRef] [PubMed]
  58. Kobayashi, T.; Miyamori, D.; Ito, M. Retrospective study on clinical value and optimal use of [18F] FDG PET/CT for inflammation of unknown origin in Japanese patients. Scientific reports 2024, 14, 28197. [Google Scholar] [CrossRef]
  59. Koreli, U. Y.; Torun, E. S.; Adaş, M. Role of Positron Emission Tomography-Computed Tomography Scan in Reaching Definite Diagnosis in Patients With Fever of Unknown Origin and Inflammation of Unknown Origin in Rheumatology Outpatient Clinic. Open access rheumatology : research and reviews 2025, 17, 25–32. [Google Scholar] [CrossRef]
  60. Yu, X.; Wang, S.; Du, N.; Zhao, H.; Chen, H. Diagnostic efficacy and necessity of 18F-FDG PET/CT in fever of unknown origin: insights from a retrospective cohort study. Frontiers in medicine 2025, 11, 1511710. [Google Scholar] [CrossRef]
  61. Greuez, C.; Lorenzo-Villalba, N.; Bessac, D. M.; Vogel, T.; Blondet, C.; Weber, J. C.; Kaltenbach, G.; Imperiale, A.; Andrès, E. Interest of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography for Fever and Inflammatory Syndrome of Unknown Origin in Elderly Patients: A Retrospective Real-Life Single-Center Study from a University Referral Hospital. Journal of clinical medicine 2025, 14, 1188. [Google Scholar] [CrossRef] [PubMed]
  62. Eynath, Y.; Halperin, E.; Buchrits, S.; Gafter-Gvili, A.; Bernstine, H.; Catalano, O.; Avni, T. Predictors for spontaneous resolution of classical FUO in patients undergoing PET-CT. Internal and emergency medicine 2023, 18, 367–374. [Google Scholar] [CrossRef] [PubMed]
  63. Takeuchi, M.; Nihashi, T.; Gafter-Gvili, A.; García-Gómez, F. J.; Andres, E.; Blockmans, D.; Iwata, M.; Terasawa, T. Association of 18F-FDG PET or PET/CT results with spontaneous remission in classic fever of unknown origin: A systematic review and meta-analysis. Medicine 2018, 97, e12909. [Google Scholar] [CrossRef]
  64. Mulders-Manders, C.; Simon, A.; Bleeker-Rovers, C. Fever of unknown origin. Clin Med (Lond) 2015, 15, 280–284. [Google Scholar] [CrossRef] [PubMed]
  65. Hess, S. FDG-PET/CT in Fever of Unknown Origin, Bacteremia, and Febrile Neutropenia. PET clinics 2020, 15, 175–185. [Google Scholar] [CrossRef]
  66. Wright, W.F.; Kandiah, S.; Brady, R.; Shulkin, B.L.; Palestro, C.J.; Jain, S.K. Nuclear Medicine Imaging Tools in Fever of unknown origin (FUO): time for a Revisit and Appropriate Use Criteria. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America 2024. [Google Scholar] [CrossRef]
  67. van Rijsewijk, N. D.; IJpma, F. F. A.; Wouthuyzen-Bakker, M.; Glaudemans, A. W. J. M. Molecular Imaging of Fever of Unknown Origin: An Update. Seminars in nuclear medicine 2023, 53, 4–17. [Google Scholar] [CrossRef]
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