Sequential [11C]Acetate and [18F]FDG PET/CT Assessment of Systemic Chronic Active Epstein–Barr Virus Disease: An Exploratory Retrospective Study

Systemic chronic active Epstein–Barr virus disease (sCAEBV) is a rare and potentially fatal disorder characterized by inflammatory manifestations and organ infiltration by EBV-infected T- or NK-cells. Although [18F]FDG PET/CT has limited utility for assessing the disease activity of sCAEBV, [11C]acetate PET/CT has not previously been evaluated in this setting. We therefore conducted this exploratory retrospective study to assess the utility of sequentially performed [11C]acetate and [18F]FDG PET/CT in sCAEBV. Five patients diagnosed with sCAEBV according to the criteria of the Research Group on Measures against Intractable Diseases, Ministry of Health, Labour and Welfare of Japan (consistent with the 2017 WHO classification) and assessed between July 2017 and December 2018 were included; patients younger than 20 years were excluded. Each patient underwent both [11C]acetate and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) on the same day. The maximum and mean standardized uptake values (SUVmax and SUVmean) of the liver and spleen and the liver-to-spleen ratio (LSR) were correlated with laboratory parameters, including alanine aminotransferase (ALT) and lactate dehydrogenase (LDH), using Spearman’s rank correlation coefficient. The LSR was compared between active and inactive cases using the Mann–Whitney U test. Twenty-one lymph node regions were assessed in each patient, and the SUVmax of detected lesions was measured. The detection rate of lymph node lesions between the two tracers was compared using McNemar’s test, and the SUVmax of lymph node lesions was compared between the two tracers and between active and inactive cases using the Mann–Whitney U test. All statistical analyses were performed using R version 4.5.3 (R Foundation for Statistical Computing, Vienna, Austria), and a p-value < 0.05 was considered statistically significant. Five patients (three men and two women; mean age 31.8 years, range 21–39 years) were included. [11C]acetate PET/CT showed significant negative correlations between spleen SUV and liver enzymes (AST, ALT, and LDH), and significant positive correlations between the LSR and all five liver enzymes tested (AST, ALT, LDH, γGTP, and ALP) (Spearman’s rank correlation coefficient; p < 0.05 for all). No significant correlations were observed with [18F]FDG PET/CT. The LSR on [11C]acetate PET/CT was numerically higher in active cases than in inactive cases, though this difference was not statistically significant (0.88 ± 0.02 vs. 0.61 ± 0.02; p = 0.20, Mann–Whitney U test). Lymph node lesion detectability did not differ significantly between the two tracers (16 vs. 12 regions; p = 0.13, McNemar’s test). In this pilot study, [11C]acetate PET/CT spleen SUV showed significant negative correlations with liver enzymes (AST, ALT, and LDH), and the LSR showed significant positive correlations with all measured liver enzymes, suggesting that [11C]acetate PET/CT reflects both hepatic and splenic involvement in sCAEBV. [11C]acetate PET/CT may therefore serve as a novel imaging biomarker for assessing disease activity in sCAEBV, warranting further investigation in larger cohorts.