ABSTRACT
Objective:To explore the role of 18F-fluorodeoxyglucose (FDG) PET/CT in early detection of therapy-associated cardiotoxicity (TACT) in lymphoma patients and to analyze the diagnostic efficacy of different evaluation criteria. Methods:Consecutive patients between November 2009 to October 2018 in Peking University Cancer Hospital were retrospectively enrolled. All patients underwent standard chemotherapy. Myocardial uptake of 18F-FDG pre- and post-treatment were analyzed by visual interpretation and semi-quantitative (maximum standardized uptake value, SUV max) methods. The value of pre-treatment SUV max-heart -post-treatment SUV max-heart (ΔSUV max), %ΔSUV max, and post-treatment SUV max-heart/SUV max-mediastinum, SUV max-heart/SUV max-liver and SUV max-heart/SUV max-background(left gluteal muscle) ratios were calculated. Receiver operating characteristic (ROC) curve analysis was performed to determine optimal cut-off values of those PET/CT imaging criteria for evaluating early TACT of lymphoma, taking electrocardiogram (ECG) positive as the end point. Independent-sample t test and χ2 test were performed. Results:A total of 274 patients (median age was 36-year old), with the male-to-female ratio of 1.85∶1, were included, and 78.1%(214/274) of them had non-Hodgkin′s lymphoma (NHL). After treatment, 55.1%(151/274)of the patients had high myocardial uptake of 18F-FDG (compared with liver uptake), 20.4%(56/274) of them had moderate myocardial uptake (between liver uptake and blood-pool uptake), and 24.5%(67/274) were with equal uptake (less than blood-pool uptake). There were significant differences in myocardial uptake between ECG-positive group ( n=71) and ECG-negative group ( n=203) ( SUV max: 7.77±4.06 vs 5.91±3.04; t=4.045, P<0.01). ROC curves showed that optimal thresholds of post-treatment SUV max-heart, Δ SUV max-heart, %ΔSUV max-heart, and post-treatment SUV max-heart/SUV max-mediastinum, SUV max-heart/SUV max-liver and SUV max-heart/SUV max-background ratios were 9.4, 4.8, 1.4, 5.0, 2.3, 7.0 respectively. The corresponding areas under the curves (AUC) were 0.653, 0.637, 0.612, 0.655, 0.649 and 0.650, respectively. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of post-treatment SUV max-heart/SUV max-background ratio were 40.85%(29/71), 82.76%(168/203), 45.31%(29/64), 80.00%(168/210) and 71.90%(197/274). Conclusion:18F-FDG PET/CT can early detect TACT in patients with lymphoma, and if using 7.0 as the threshold of post-treatment SUV max-heart/SUV max- background ratio, the specificity and negative predictive value of 18F-FDG PET/CT for early prediction of TACT are up to 80%.
ABSTRACT
Objective To study the effects of chimeric B7 antibodies on mononuclear cells from patients with ankylosing spondylitis (AS).Methods Chimeric antibodies of ch4E5 and chlD1 against B7 with a final concentration of 5 μg/ml were respectively added into culture media of mononuclear cells from patients with AS.Two other groups including huIgG-treated and untreated culture medium of mononuclear cells from patients with AS were set up as the controls.The culture medium of mononuclear cells from healthy subjects were prepared as normal control group.The disparities of mononuclear cell death in culture among each group were analyzed by using micro-lymphocyte cytotoxicity test (MLCT).The expression of membrane molecules were analyzed by FCM.The concentrations of cytokines in culture media were measured by ELISA.Results Both groups treated with the chimeric antibody showed lower scores for cell death than untreated group as indicated by MLCT (P＜0.01).FCM analysis demonstrated that both CD4/CD8 ratio (P ＜0.05) and membrane expression of CD154 (P＜0.01) decreased in chimeric antibody treated groups,but the number of CD4+CD25high Treg cells (P＜0.01) increased as compared with those in untreated group.The concentrations of IL-2 and TNF-α were down-regulated (P＜0.05) in chimeric antibody treated groups,while IL-4 and TGF-β were up-regulated (P＜0.02) as compared with those in untreated group.Conclusion Chimeric B7 antibodies might affect the expression of T cell membrane molecules and the cytokine production by mononuclear cells through B7/CD28 and CD4O/CD154 signaling pathways in patients with AS.