Head-to-head comparative study on detection of occult infection using 18F FDG Labelled Leukocytes PET/CT scan and 18F FDG PET/CT scan

Introduction: Differentiating infection and sterile inflammation is the main clinical concern of clinicians as they are closely related to each other. Though 18F FDG PET/CT imaging being widely used, the main disadvantage of this scan is lack of specificity to discriminate aseptic from septic inflammation. 18F FDG Labelled Leukocytes (WBC PET/CT) scan is a promising tool for the accurate diagnosis of infection owing to its high specificity. The aim of this study is to provide a head-to-head comparison of WBC PET/CT scan and 18F FDG PET/CT scan in the diagnosis of occult infections and to assess the incremental value of WBC PET/CT over 18F FDG PET/CT scan.

Methods: This prospective observational diagnostic accuracy study was conducted at Fortis Memorial Research Institute, Gurugram, in the department of Nuclear Medicine. 38 patients with fever of unknown origin or suspected periprosthetic infection and raised CRP and TLC were included in the study. Patients with favourable clinical response to antibiotics were not included in the study. All the patients underwent both scans using a standard protocol on two different days. Images of both the scans were evaluated by both visual analysis based on uptake intensity and quantitative grading based on lesion to background SUVmax values. Final diagnosis was made by histopathological, microbiological analysis or clinical-radiological work-up. ROC curve analysis was done to calculate the optimal SUVmax threshold cut-off for both imaging modalities.

Results: 38 patients were included in the study with mean clinical follow up of 10 months. 34 foci of suspected infection were found in 30 patients by either 18F FDG PET/CT or 18F FDG labelled WBC PET/CT scan. No abnormal uptake of either 18F FDG or 18F FDG WBC was seen in 8 patients. Of the 34 suspicious infected foci, 21 were proven positive for infection (17/21 sites by the histopathological / microbiological culture and the rest 4/21 sites by clinical / radiological work-up). 13 suspected foci were proven non infective (11/13 sites proven by histopathological / microbiological culture while rest 2/13 sites were considered non infective by clinical/radiological work-up). Overall, significantly higher diagnostic accuracy was demonstrated with WBC PET/CT as compared to 18F FDG PET/CT for the detection of infection (p<0.05). The highest diagnostic accuracy of WBC PET/CT scan was reported with grade 1b for visual as well as of quantitative analysis and grade 2 for both visual and quantitative analysis for 18F FDG PET CT. At the grade of highest diagnostic accuracy, NPV of WBC PET/CT (visual, 94.44%; quantitative, 94.74%) was documented higher than FDG PET/CT (visual, 89.47%; quantitative, 88.23%).

Based on ROC analysis, optimal threshold cut off for SUVmax for differential diagnosis of the infection and aseptic inflammation was 3.75 for WBC PET/CT and 5.85 for 18F FDG PET/CT scan. Using this threshold, the sensitivity and specificity of WBC PET/CT was 95.2% and 85.7%, respectively, which were both higher than the sensitivity (85.7%) and specificity (81%) of 18F FDG PET/CT scan.

Conclusions: Head-to-head comparison shows that WBC PET/CT has comparatively higher diagnostic accuracy along with an incremental value over 18F FDG PET/CT for the diagnosis of occult infection.