Incremental Value of 18F-FDG–Labeled Leukocytes PET/CT Over 18F-FDG PET/CT Scan in the Detection of Occult Infection
Authors: Manda Divya , Thakral Parul , Sen Ishita , Das Subha Shankar , CB Virupakshappa , Malik Dharmender 
Published: July 2022

Purpose
Differentiating infection and sterile inflammation is the main clinical concern of clinicians as they are closely related to each other. Although 18F-FDG PET/CT imaging is widely used, its main disadvantage is its lack of specificity to discriminate aseptic from septic inflammation. 18F-WBC PET/CT scan is a promising tool for the accurate diagnosis of infection owing to its high specificity. The aim of the present study is to determine the utility of 18F-WBC PET/CT in the diagnosis of occult infections and to assess its incremental value over routine 18F-FDG PET/CT scan.

Patients and Methods
This prospective observational diagnostic accuracy study included 33 patients with fever of unknown origin or suspected periprosthetic infection and raised C-reactive protein and total leukocyte count. All the patients underwent both 18F-WBC PET/CT scan and 18F-FDG PET/CT scan using a standard protocol on 2 different days. Images of both the scans were evaluated by both visual analyses based on uptake intensity and quantitative grading based on lesion-to-background SUVmax values. For interpretation of FDG PET/CT images, visual scoring of grade 0 (undetectable or no uptake), grade 1a (less than liver uptake), grade 1b (equivalent to liver uptake), grade 2 (higher than liver uptake), and grade 3 (higher than cerebellum uptake) was used. 18F-WBC PET/CT images were also interpreted visually as grade 0 (undetectable or no uptake), grade 1a (significantly less than lumbar vertebrae or liver uptake for truncal lesions, and in case of extremity lesion slightly higher than neighboring soft tissue uptake or less than neighboring bone marrow uptake), grade 1b (equivalent to liver or lumbar vertebrae uptake for truncal lesions, and in case of extremity lesion significantly higher than neighboring soft tissue uptake or higher than neighboring bone marrow uptake), grade 2 (higher than liver or bone marrow uptake), and grade 3 (higher than twice the liver or bone marrow uptake). Similarly, a quantitative grading was also done based on lesion-to-background SUVmax using a circular region of interest manually drawn. For both 18F-FDG and 18F-WBC PET/CT, the lesion-to-background ratio of <1.5 was recorded as grade 0, 1.5–2.5 as grade 1a, 2.5–3.5 as grade 1b, 3.5–4.5 as grade 2, and >4.5 as grade 3. Final diagnosis was made by histopathological, microbiological analysis, or clinical-radiological workup.

Results
Twenty-nine foci of suspected infection were found in 25/33 patients by either 18F-FDG PET/CT or 18F-WBC PET/CT scan. No abnormal uptake of either 18F-FDG or 18F-FDG WBC scan was seen in 8 patients. There was a concordance of 18F-FDG PET/CT and 18F-WBC PET/CT in 28 sites each using grade 1b of visual and quantitative analysis, respectively. Of the 29 suspicious infected foci, 18 were proven positive for infection (14/18 sites by the histopathological/microbiological culture and the rest 4/18 sites by clinical/radiological workup). Culture of aspirates or biopsy from 11/29 suspicious sites was proven noninfective. Seven of 11 suspicious sites were proven noninfective by clinical/radiological workup. The mean clinical follow-up was 8 months (1–15 months).
Overall significantly higher diagnostic accuracy was demonstrated with 18F-WBC PET/CT in comparison to 18F-FDG PET/CT for the detection of infection (P < 0.05). The highest diagnostic accuracy of 18F-WBC PET/CT scan was reported with both grade 1b of visual as well as of quantitative analysis (lesion-to-background SUVmax, 2.5–3.5) and grade 2 for both visual and quantitative analysis for 18F FDG PET/CT.

Conclusions

18F-WBC PET/CT has a higher diagnostic accuracy over 18F-FDG PET/CT for the diagnosis of occult infection.