The Preclinical And Clinical Study Of¹⁸F-FDGPET/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 thedifference of¹⁸F-FDG uptake in different pathological types of lung cancer cell,providing a theoretical basis and evidence for¹⁸F-FDG PET/CT imaging monitoringeffective 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 and72h）. In uptake experiments,¹⁸F-FDG incubated with different lung cancercells at different time （30、60、90、120and180min） and measured gamma countextracellular fluid and cells with γ count in each group. By the methods ofimmunofluorescence and real-time PCR detected the expression of the glucosetransporter protein-1（Glut-1） and hexokinase II （HKII）. The statistical analysis weretwo-way ANOVA,t test or repeated-measurement.Result: MTT and flow cytometry showed that the different lung cancer cells had ahigher sensitivity with CTX. In¹⁸F-FDG uptake studies in vitro, it showed that thedifference has statistical significance between incubation time and¹⁸F-FDG uptake（F=6.39,P<0.01）. In control group, the¹⁸F-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 cellshave higher expression of Glut-1and HKII. According to real-time PCR, it wasobserved that the difference of expression were statistical significance between Glut-1and HKII （F=5.895and113.567, P<0.01）. Glut-1were SK-MES-1> A549>NCI-H446> NCI-H460; HKIIwere NCI-H460> A549> SK-MES-1> NCI-H446. Itshowed that HKII and¹⁸F-FDG uptake had the same tendency.Conclusion: This study showed that different pathological types of lung cancer cells had a difference of¹⁸F-FDG uptake. HKII may play an important role in¹⁸F-FDGuptake. Objective: This study was aimed to evaluate the ability of¹⁸F-FDG PET/CT earlymonitoring of lung cancer response to chemotherapy. A series experiments includingPET/CT imaging, biodistribution and tumor volume were performed to providing basis andtheoretic foundation for clinical.Methods: BALB/c nude mice were used to establish tumor-bearing models （NCI-H446and NCI-H460in the left upper; A549and SK-MES-1in the right upper） and were dividedinto two groups: control group and experimental group （24h,48h,72h and168h）. When thelong diameter of tumor arrived to1.0±0.2cm, nude mice tumor bearing were injectedintraperitoneally with a single high dose cyclophosphamide （100mg/kg）, PET/CT imagingwas performed at1h post-injection with¹⁸F-FDG via tail vein. The biodistribution wasobserved in major organs and blood at0h,24h48h72h and168h in different groups. Inaddition, we measured the long diameter and short diameter in tumor at different timebetween before pro-treatment and post-treatment （24h,48h,72h and168h）. The t-testwas compared between before treatment and after treatment for statistical analysis.Bivariate correlation analysis and analysis of variance were used through SPSS20.0software, and P＜0.05was considered significant.Results: The result of¹⁸F-FDG PET/CT imaging showed that the¹⁸F-FDG uptake of tumorhad a higher level in control group，but the¹⁸F-FDG uptake of tumor was decreased intreatment group. For the biodistribution studies, we knew that the experiment group waslower than control group in¹⁸F-FDG uptake of tumor. The results of T, T/B and T/M indifferent groups showed that there was statistically significant with T/B （72h and168h） inNCI-H446（P<0.05）; T（168h） and T/M （168h） in NCI-H460（P<0.05）; T/B（24h,48h and168h） in A549（P<0.05）; T（48h and72h） in SK-MES-1（P<0.05）. As a results of controlgroup, T, T/B and T/M in NCI-H446were3.2±0.49,2.73±0.9and1.17±0.54; T, T/B andT/M in NCI-H460were6.43±3.47,5.64±2.89and3.57±2.59; T, T/Bå’ŒT/M in A549were 4.54±1.05,1.65±0.67and1.04±0.39ï¼›T, T/B and T/M in SK-MES-1were3.23±0.5,3.53±1.2and1.09±0.74. The correlation analysis showedthat 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 volumeincreased in NCI-H446and SK-MES-1, the difference （48h,72h and168h） had statisticalsignificance （P<0.01） between control group and experimental group.Conclusion: Clinical PET/CT imaging had the applicability and feasibility for monitoringsmall animal model,¹⁸F-FDG PET/CT can be early monitoring for effective treatment oftumor in the different lung cancer cells and detecting to reduction of¹⁸F-FDG uptake intumor as early as48h after treatment. Objective: To investigate the efficacy of¹⁸F-FDG PET/CT in monitoring lung cancerpatients after therapy with staging and restaging, evaluation of therapy and prediction ofsurvival.Methods: We retrospectively analyzed43patients with clearly diagnosed lung cancer andperformed PET/CT scanners in Wuhan Union Hospital. All the patients were performed atleast three PET/CT scanners, which were before therapy （from Jan16,2004to Dec4,2009）, at the early stage of treatment （from Apr26,2005to Apr21,2011） and at the end oftherapy （from Dec28,2006to Fer15,201）. The TNM classification system for staging andrestaging of lung cancer is a vital guide for determining treatment and prognosis. ResponseEvaluation Criteria in Solid Tumors1.1（RECIST） guidelines was used as criteria forevaluation of therapy response, and all the patients were evaluated the tolerance rate withKPS scores. The absolute value of SUVmax change （△SUVmax） and the decrease rate （%）before and after the early and the end of therapy were used as the evaluation index. Thedecreased rate of70%after the early treatment was chosen as a cut-off for evaluation of theclinical prognosis, and this value was obtained from receiver-operating characteristic curve.Survival analysis and prognosis evaluation were performed with Kaplan-Meier and Coxregression analysis.Results: A total of43patients were included. The median age was24days （range,25to83years） and mean follow-up was39months （range,12to89months）. It is significant thatTNM staging as a cutoff after the final treatment （R2=13.659，P＜0.01）. Overall the median,3-years and5-years survival were5-year were46.71±12.79months,11.63%and2.33%in0staging;87months,2.33%and2.33%in I staging;57.33±27.54months,4.65%and2.33%in II staging;18.5±9.19months,0%and0%in III staging;39±18.9months,39.53%and11.63%in IV staging. In the different group of CR, PR, SD and PD, Δ SUVmax were9.42±5.37,5.25±4.01,4.25±3.41and4.62±4.68after the early treatment, and8.27±6.97; 2.5±1.55,3±3.8and5.68±4.46after the final treatment. There had significant differencebetween these groups （F=3.351,P＜0.05）. Statistical difference were also seen in thedecreased rate of SUVmax in the groups of before, after the early and the end of treatment（F=21.991, P＜0.01）. When70%was used as a cut-off and divided into two groups, therehad much difference for the survival time between the two groups. KPS scoring was also asignificant prognostic factor in the different stage of treatment （R2=21.163, P＜0.01, beforetreatment; R2=15.879, P＜0.01, after the early treatment; R2=15.879, P＜0.01; at the end ofthe 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 SUVmaxafter the end of the treatment （R2=1.44，P＜0.01）, the SUVmax of the original lesion beforetreatment （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 withstaging and restaging, evaluation of treatment efficacy and prediction of prognosis. KPSscoring and RECIST are also important factors for clinical evaluation of prognosis. Thedecreased rate of70%after the early treatment may be a good cut-off for the evaluation oftherapy response and prognosis in lung cancer patients.