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Metabolic reprogramming is a hallmark of tumors. Tumors own unique metabolic patterns in different stages of their occurrence and development. The stable isotope metabolic flux analysis technology uses stable isotope to trace the metabolites in tumors and crystallize tumor metabolism network. Stable isotope metabolic flux analysis is a useful tool for studying tumor metabolism, which can determine the nutritional sources, find the metabolic liabilities, confirm the metabolic pattern of tumors, and discover new mechanisms of tumor metabolic reprogramming, thus providing theoretical bases for imaging, diagnosis, treatment and evaluation of tumor. This article reviews the applications of stable isotope flux analysis in tumor metabolic reprogramming.
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Objective:To assess the imaging characteristics of muscle FDG metabolism, tumor incidence, and pulmonary interstitial changes in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody positivity in 18F-FDG PET/CT imaging, and the value of 18F-FDG PET/CT in differentiating anti-MDA5 antibody positive dermatomyositis. Methods:From June 2016 to July 2019, the PET/CT images of 75 patients with dermatomyositis (21 males, 54 females, age (52.3±14.3) years; 34 anti-MDA5 antibody positive and 41 anti-MDA5 antibody negative) and 30 healthy controls (10 males, 20 females; age (53.5±11.8) years) were retrospectively analyzed in Renji Hospital, School of Medicine, Shanghai Jiao Tong University. The SUV max of muscle was measured and the mean of SUV max (mSUV max) was calculated. Statistics of patients with dermatomyositis complicated with neoplastic lesions and the SUV max of pneumonia lesions in patients with dermatomyositis complicated with interstitial pneumonia was determined. Independent sample t test, one-way analysis of variance, Student-Newman-Keuls (SNK) test and χ2 test were used to analyze data. The ROC curve analysis was used to analyze the diagnostic efficacy of mSUV max for the differential diagnosis of anti-MDA5 antibody positive dermatomyositis. Results:The muscle mSUV max of the control group, anti-MDA5 antibody positive and negative groups were 0.39±0.05, 0.66±0.21 and 0.87±0.29 ( F=39.93, P<0.001), respectively. The muscle mSUV max of dermatomyositis patients was increased compared with healthy controls ( q values: 6.76, 12.63, both P<0.001), and the muscle mSUV max of anti-MDA5 antibody negative was higher than positive ( q=5.79, P<0.001). The AUC was 0.74, and the cut-off value of muscle mSUV max was 0.75 with the accuracy of 74.7%(56/75). Of 41 patients with negative anti-MDA5 antibody, there were 6 (14.6%) had malignant tumor, while there was no malignant tumor in patients with positive anti-MDA5 antibody (0/34; χ2=5.41, P=0.020). There were 11 patients (26.8%, 11/41) with anti-MDA5 antibody negative dermatomyositis complicated with interstitial pneumonia and 33 patients (97.1%, 33/34) with anti-MDA5 antibody positive dermatomyositis complicated with interstitial pneumonia ( χ2=37.81, P<0.001). FDG metabolism in anti-MDA5 antibody positive patients was higher than that in anti-MDA5 antibody negative patients (lesion SUV max: 3.65±1.83 and 2.38±1.27; t=2.13, P=0.039). Conclusions:The muscle FDG metabolism of anti-MDA5 antibody positive dermatomyositis patients is higher than that of healthy controls, but lower than that of anti-MDA5 antibody negative patients. The incidence of neoplastic lesions in patients with positive anti-MDA5 antibody is lower than that in patients with negative anti-MDA5 antibody. The proportion and severity of interstitial pneumonia are higher in patients with positive anti-MDA5 antibody than in those with negative anti-MDA5 antibody. 18F-FDG PET/CT has certain value on identifying anti-MDA5 antibody positive dermatomyositis.
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Objective To investigate the relationship between 18F-fluorodeoxyglucose (FDG) PET/CT metabolic parameters of colorectal cancer (CRC) and liver metastasis.Methods A total of 98 CRC patients (66 nales,32 females,average age:(64+13) years) from January 2012 to October 2016 in Shanghai Renji Hospital were enrolled in this retrospective study.All patients underwent 18F-FDG PET/CT and had not received any treatment before surgery.The relationships between clinical pathological results,metabolic parameters and liver metastasis were analyzed.Data were analyzed usingx2 test and logistic regression analysis.Results Patients were divided into two groups,78 without liver metastasis,20 with liver metastasis.Univariate analysis showed that the tumor primary location(x2=5.983),T stage(x2=6.447),serum carcinoembryonic antigen (CEA) levels(x2 =5.501),metabolic tumor volume (MTV;x2 =6.282) and total lesion glycolysis (TLG;x2=9.046) were significantly different between the two groups (all P＜0.05).Multiple factor analysis showed that the tumor primary location,T stage,serum CEA levels,MTV and TLG (odds ratio (OR):0.059-7.575)were independent risk factors of CRC liver metastasis,and MTV and TLG were negatively correlated with liver metastasis.Conclusions Tumor primary location,T stage,serum CEA levels,MTV and TLG are independent risk factors of CRC liver metastasis.MTV and TLG are negatively correlated with liver metastasis.
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Objective To evaluate the predictive value of tumor metabolic indexes measured by 18F-FDG PET/CT in recurrence of stage Ⅰ NSCLC after surgery.Methods A total of 85 patients (44 males,41 females,age (62.46± 10.38) years) in Shanghai Renji Hospital with stage Ⅰ NSCLC,who underwent 18F-FDG PET/CT and subsequent surgical resection,were retrospectively enrolled from April 2006 to December 2011.Gender,age,tumor size,pathology,SUVmax,MTV and TLG of the primary tumor were selected as variables.ROC curve analysis was used to analyze the cut off value.The prognostic significance of parameters for recurrence-free survival (RFS) was evaluated by univariate and multivariate analyses.Survival analysis was analyzed by Kaplan-Meier method.Results During follow-up period,tumor recurrence occurred in 21 patients (24.7％,21/85) and 11 patients (12.9％,11/85) died.The median follow-up period was 44 months.The median values of SUVmax,MTV and TLG were 4.100,3.048 cm3 and 7.970,respectively.Cut off values of SUVmax,MTV and TLG were 7.115,4.701 cm3 and 12.015 according to ROC curve analysis.Univariate Cox analysis showed that SUVmax(x2 =22.091),MTV (x2 =4.941) and TLG(x2 =10.488) were associated with RFS(all P＜0.05).But gender,age,tumor size,and pathology were not independent risk factors of recurrence (x2=0.248-3.888,all P＞0.05).Multivariate Cox analysis revealed that SUVmax(=16.902,HR=15.426,P＜0.05) and TLG (x2=6.029,HR=4.054,P＜0.05) were independent prognostic factors for recurrence.Kaplan-Meier survival analysis showed that the period of RFS in high SUVmax (＞ 7.115) group (x2=32.545,P＜0.05) and in high TLG (＞12.015) group (x2=12.665,P＜0.05) were lower than those in low SUVmax group and low TLG group.Conclusion The SUVmax and TLG measured by 18F-FDG PET/CT have significant value for predicting the recurrence of stage Ⅰ NSCLC.