Fever of unknown origin: prospective comparison of [18F]FDG imaging with a double-head coincidence camera and gallium-67 citrate SPET

Abstract

Gallium-67 citrate is currently considered as the tracer of first choice in the diagnostic workup of fever of unknown origin (FUO). Fluorine-18 2'-deoxy-2-fluoro-D-glucose (FDG) has been shown to accumulate in malignant tumours but also in inflammatory processes. The aim of this study was to prospectively evaluate FDG imaging with a double-head coincidence camera (DHCC) in patients with FUO in comparison with planar and single-photon emission tomography (SPET) 67Ga citrate scanning. Twenty FUO patients underwent FDG imaging with a DHCC which included transaxial and longitudinal whole-body tomography. In 18 of these subjects, 67Ga citrate whole-body and SPET imaging was performed. The 67Ga citrate and FDG images were interpreted by two investigators, both blinded to the results of other diagnostic modalities. Forty percent (8/20) of the patients had infection, 25% (5/20) had auto-immune diseases, 10% (2/20) had neoplasms and 15% (3/20) had other diseases. Fever remained unexplained in 10% (2/20) of the patients. Of the 20 patients studied, FDG imaging was positive and essentially contributed to the final diagnosis in 11 (55%). The sensitivity of transaxial FDG tomography in detecting the focus of fever was 84% and the specificity, 86%. Positive and negative predictive values were 92% and 75%, respectively. If the analysis was restricted to the 18 patients who were investigated both with 67Ga citrate and FDG, sensitivity was 81% and specificity, 86%. Positive and negative predictive values were 90% and 75%, respectively. The diagnostic accuracy of whole-body FDG tomography (again restricted to the aforementioned 18 patients) was lower (sensitivity, 36%; specificity, 86%; positive and negative predictive values, 80% and 46%, respectively). 67Ga citrate SPET yielded a sensitivity of 67% in detecting the focus of fever and a specificity of 78%. Positive and negative predictive values were 75% and 70%, respectively. A low sensitivity (45%), but combined with a high specificity (100%), was found in planar 67Ga imaging. Positive and negative predictive values were 100% and 54%, respectively. It is concluded that in the context of FUO, transaxial FDG tomography performed with a DHCC is superior to 67Ga citrate SPET. This seems to be the consequence of superior tracer kinetics of FDG compared with those of 67Ga citrate and of a better spatial resolution of a DHCC system compared with SPET imaging. In patients with FUO, FDG imaging with either dedicated PET or DHCC should be considered the procedure of choice.

EANM/SNMMI Guideline for18F-FDG Use in Inflammation and Infection

“…• Evaluation of fever of unknown origin (FUO) (29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44), including true FUO (defined according to the criteria of Durack and Street (44)), postoperative fever and recurrent sepsis, immunodeficiency (both induced and acquired)-related FUO, neutropenic fever, and isolated acute-phase inflammation markers (persistently raised C-reactive protein and/or erythrocyte sedimentation rate).…”

Nuclear Imaging for Classic Fever of Unknown Origin: Meta-Analysis

“…Typically, studies retrospectively assessed nuclear imaging tests as second-or third-level examinations, performed after diagnostic workup that was not standardized in each study. Eight studies (19%) were prospective: 1 study adopted a standardized workup algorithm (28), and 3 studies specified mandatory preimaging tests (29)(30)(31) as selection criteria, one of which routinely performed thoracoabdominal contrast-enhanced CT (31). The average preimaging disease duration ranged from 5 to 41 wk.…”

Imaging of Inflammation by PET, Conventional Scintigraphy, and Other Imaging Techniques

“…Therefore, 67 Ga imaging has several disadvantages for patients: it is timeconsuming, must be repeated, and has a relatively high radiation burden. In a study of 58 patients with FUO, Meller et al showed that 67 Ga scintigraphy had a diagnostic yield nearly equivalent to that of 18 F-FDG PET (74). However, in that study, 18 F-FDG scanning was performed with a coincidence camera instead of a dedicated full-ring PET scanner, which is superior for PET.…”