The Preclinical And Clinical Study Of18F-FDG PET/CT In Evaluation Of Treatment Effect And Monitoring Recurrence And Metastasis In Patients With Lung Cancer

Objective:The aim of the investigate was to explore the sensitivity of CTX and the difference of 18F-FDG uptake in different pathological types of lung cancer cell, providing a theoretical basis and evidence for 18F-FDG PET/CT imaging monitoring effective therapy in lung cancer.Methods:There are four different pathological types of lung cancer cell lines: NCI-H446 (human small cell lung cancer),NCI-H460 (large cell lung cancer),A549 (human lung adenocarcinoma) and SK-MES-1 (human lung squamous carcinoma). The sensitivity of CTX was tested by MTT and flow cytometry at different time (24h, 48h and 72h). In uptake experiments,18F-FDG incubated with different lung cancer cells at different time (30,60,90,120 and 180min) and measured gamma count extracellular fluid and cells withγcount in each group. By the methods of immunofluorescence and real-time PCR detected the expression of the glucose transporter protein-1 (Glut-1) and hexokinaseⅡ(HKⅡ). The statistical analysis were two-way ANOVA,t test or repeated-measurement.Result:MTT and flow cytometry showed that the different lung cancer cells had a higher sensitivity with CTX. In 18F-FDG uptake studies in vitro, it showed that the difference has statistical significance between incubation time and 18F-FDG uptake (F=6.39,P<0.01). In control group, the 18F-FDG uptake were:NCI-H460> A549> SK-MES-1> NCI-H446, and there was statistical significance in different cells (F=12.46,P<0.01). The immunofluorescence results showed that the lung cancer cells have higher expression of Glut-1 and HKⅡ. According to real-time PCR, it was observed that the difference of expression were statistical significance between Glut-1 and HKII (F=5.895 and 113.567, P<0.01). Glut-1 were SK-MES-1> A549> NCI-H446> NCI-H460; HKⅡwere NCI-H460> A549> SK-MES-1> NCI-H446. It showed that HKII and 18F-FDG uptake had the same tendency.Conclusion:This study showed that different pathological types of lung cancer cells had a difference of 18F-FDG uptake. HKII may play an important role in 18F-FDG uptake. Objective:This study was aimed to evaluate the ability of 18F-FDG PET/CT early monitoring of lung cancer response to chemotherapy. A series experiments including PET/CT imaging, biodistribution and tumor volume were performed to providing basis and theoretic foundation for clinical.Methods:BALB/c nude mice were used to establish tumor-bearing models (NCI-H446 and NCI-H460 in the left upper; A549 and SK-MES-1 in the right upper) and were divided into two groups:control group and experimental group (24h,48h,72h and 168h). When the long diameter of tumor arrived to 1.0±0.2cm, nude mice tumor bearing were injected intraperitoneally with a single high dose cyclophosphamide (100mg/kg), PET/CT imaging was performed at lh post- injection with F-FDG via tail vein. The biodistribution was observed in major organs and blood at Oh,24h 48h 72h and 168h in different groups. In addition, we measured the long diameter and short diameter in tumor at different time between before pro-treatment and post-treatment (24h,48h,72h and 168h). The t-test was compared between before treatment and after treatment for statistical analysis. Bivariate correlation analysis and analysis of variance were used through SPSS 20.0 software, and P<0.05 was considered significant.Results:The result of 18F-FDG PET/CT imaging showed that the 18F-FDG uptake of tumor had a higher level in control group, but the 18F-FDG uptake of tumor was decreased in treatment group. For the biodistribution studies, we knew that the experiment group was lower than control group in 18F-FDG uptake of tumor. The results of T, T/B and T/M in different groups showed that there was statistically significant with T/B (72h and 168h) in NCI-H446 (P<0.05); T(168h) and T/M (168h) in NCI-H460 (P<0.05); T/B(24h,48h and 168h) in A549 (P<0.05); T(48h and 72h) in SK-MES-1 (P<0.05). As a results of control group, T, T/B and T/M in NCI-H446 were 3.2±0.49,2.73±0.9 and 1.17±0.54; T, T/B and T/M in NCI-H460 were 6.43±3.47,5.64±2.89 and 3.57±2.59; T, T/B和T/M in A549 were 4.54±1.05,1.65±0.67 and 1.04±0.39; T, T/B and T/M in SK-MES-1 were 3.23±0.5, 3.53±1.2 and 1.09±0.74. The correlation analysis showed that it had a good correlation between the tumor (%ID/g) and post-treatment in A549 (R2=0.7818, P<0.05). The yieid of difference in tumor volume showed that tumor volume increased in NCI-H446 and SK-MES-1, the difference (48h,72h and 168h) had statistical significance (P<0.01) between control group and experimental group.Conclusion:Clinical PET/CT imaging had the applicability and feasibility for monitoring small animal model, 18F-FDG PET/CT can be early monitoring for effective treatment of tumor in the different lung cancer cells and detecting to reduction of 18F-FDG uptake in tumor as early as 48 h after treatment. Objective:To investigate the efficacy of 18F-FDG PET/CT in monitoring lung cancer patients after therapy with staging and restaging, evaluation of therapy and prediction of survival.Methods:We retrospectively analyzed 43 patients with clearly diagnosed lung cancer and performed PET/CT scanners in Wuhan Union Hospital. All the patients were performed at least three PET/CT scanners, which were before therapy (from Jan 16,2004 to Dec 4, 2009), at the early stage of treatment (from Apr 26,2005 to Apr 21,2011) and at the end of therapy (from Dec 28,2006 to Fer 15,201). The TNM classification system for staging and restaging of lung cancer is a vital guide for determining treatment and prognosis. Response Evaluation Criteria in Solid Tumors 1.1 (RECIST) guidelines was used as criteria for evaluation of therapy response, and all the patients were evaluated the tolerance rate with KPS scores. The absolute value of SUVmax change (2SUVmax) and the decrease rate (%) before and after the early and the end of therapy were used as the evaluation index. The decreased rate of 70% after the early treatment was chosen as a cut-off for evaluation of the clinical prognosis, and this value was obtained from receiver-operating characteristic curve. Survival analysis and prognosis evaluation were performed with Kaplan-Meier and Cox regression analysis.Results:A total of 43 patients were included. The median age was 24 days (range,25 to 83 years) and mean follow-up was 39 months (range,12 to 89 months). It is significant that TNM staging as a cutoff after the final treatment (R2=13.659, P<0.01). Overall the median, 3-years and 5-years survival were 5-year were 46.71±12.79 months,11.63% and 2.33% in 0 staging; 87 months,2.33%and 2.33% inⅠstaging; 57.33±27.54 months,4.65% and 2.33% inⅡstaging; 18.5±9.19 months,0% and 0% inⅢstaging; 39±18.9 months,39.53% and 11.63% inⅣstaging. In the different group of CR, PR, SD and PD,ΔSUVmax were 9.42±5.37,5.25±4.01,4.25±3.41 and 4.62±4.68 after the early treatment, and 8.27±6.97; 2.5±1.55,3±3.8 and 5.68±4.46 after the final treatment. There had significant difference between these groups (F=3.351,P<0.05). Statistical difference were also seen in the decreased rate of SUVmax in the groups of before, after the early and the end of treatment (F=21.991,P<0.01). When 70% was used as a cut-off and divided into two groups, there had much difference for the survival time between the two groups. KPS scoring was also a significant prognostic factor in the different stage of treatment (R2=21.163, P<0.01, before treatment; R2=15.879, P<0.01, after the early treatment; R2=15.879, P<0.01; at the end of the treatment). Some factors may be the useful factors from the COX regression analysis, and they were the serum CEA level (R2=0.00000089,P<0.01), the decreased rate of SUVmax after the end of the treatment (R2=1.44, P<0.01), the SUVmax of the original lesion before treatment (R2=2605.573,P<0.05) and the metastasis outside of lung after the final treatment (R2=6.483, P<0.05).Conclusion:18F-FDG PET/CT plays an important role in the lung cancer patients with staging and restaging, evaluation of treatment efficacy and prediction of prognosis. KPS scoring and RECIST are also important factors for clinical evaluation of prognosis. The decreased rate of 70% after the early treatment may be a good cut-off for the evaluation of therapy response and prognosis in lung cancer patients.