| ObjectiveThe aim of this study was to evaluate early response to treatment of colon cancer with 18F-FDG PET/CT from two aspects, preclinical research which consisted cells experiments and animals experiments and clinical study, respectively, as follows:1. Preclinical research: The aim of this part was to evaluate early response to Fluorouracil ( FU ) treatment of nude mice bearing colon cancer through experiments of the level of cells and animals for providing a foundation reference of applying [18-F]fluoro-2-deoxy-D-glucose ( 18F-FDG ) to evaluate early effect to treatment of colon cancer in clinical.2. Clinical study: The aim of this part was to evaluate the monitoring value of recurrence and/or metastasis and prognostic performance of 18F-FDG PET/CT in patients of postoperative colon cancer.Methods1. Preclinical research: ( 1 ) The activity of colon cancer Lovo cells was tested by MTT assay after they were treated by 5 different concentrations FU ( 0.02μg/ml, 0.2μg/ml, 2μg/ml, 20μg/ml, 200μg/ml )at different times ( 2 h, 12 h, 24 h, 48 h ). ( 2 ) The 1 h 18F-FDG uptake rate of Lovo cells was measured after they were treated by 3 different concentrations FU ( 0.2μg/ml, 2μg/ml, 20μg/ml ) at different times ( 2 h, 12 h, 24 h, 48 h ). ( 3 ) BALB/c nude mice colon cancer subcutaneous models were established and were divided into experimental and control groups. In experimental groups, nude mice bearing tumor were injected intraperitoneally with a single high dose FU (165 mg/Kg, 0.2 ml), and in the control group, nude mice bearing tumor were injected intraperitoneally with equal volume saline. Nude mice bearing tumor were fasted ( with water ) about 20 h in control group and all experimental groups ( 2 h, 24 h, 48 h and 168 h ), and then they were injected with 18F-FDG 0.1 mCi ( 0.2 ml ) via tail vein. When the tracer was injected about 1 h the blood of nude mice was collected from orbital venous plexus and then they were killed by cervical in order to implement biodistribution studies. ( 4 ) Five nude mice bearing tumor with long diameter 8 ~ 10 mm were fasted but given water about 20 h and then were imaged by PET/CT after they were injected with 18F-FDG 0.2 mCi ( 0.2ml ) about 1 h. ( 5 ) Eight nude mice bearing tumor with long diameter 5 ~ 8 mm were randomly divided into two groups, experimental group and control group, respectively. The long and short diameter of tumors of all mice were measured before treatment, and then they were also measured once every 2 days after the mice were treated until the 8 days after treatment ( the way of treatment was the same as before. ).2. Clinical study: A total of 78 patients of postoperative colon cancer, men 46 and women 32, who took an examination in the PET/CT center of Union Hospital between April 2004 and November 2009, were included in this retrospective study. The diagnostic results of PET/CT and conventional imaging ( such as CT, MRI and so on ) were analyzed and compared with histopathological diagnosis and/or long-term clinical follow-up data ( follow-up time range from 3 months to 58 months ), respectively. The clinical prognostic outcomes of patients in true positive group and in true negative group decided by PET/CT were compared. The maximum value of all SUVmax values of each patient was selected and the patients were divided into two subgroups taking mean value and median of all above maximum values as a cutoff, respectively, and then the clinical prognostic outcomes of the corresponding two subgroups were compared.Results1. Preclinical research: ( 1 ) The results of MTT showed that when cells were treated with 5 different concentrations FU for 2 hours, there was no significant difference in cells viability between 5 experimental groups and control group. When cells were treated for 12 hours,there was no significant difference between a experimental group ( 0.02μg/ml ) and control group, but there were significant differences between the remaining 4 experimental groups and control group ( P values<0.05 ). When cells were treated for 24 hours, there was no significant difference between 2 experimental groups ( 0.02μg/ml and 0.2μg/ml ) and control group, but there were significant differences between remaining 3 experimental groups and control group ( P values<0.05 ). When cells were treated for 48 hours, there were significant differences between 5 experimental groups and control group ( P values<0.05 ). ( 2 ) The results of 18F-FDG uptake in vitro showed that when the cells were treated with FU for 2 hours, there was no significant statistic difference in 18F-FDG uptake rate of cells between all experimental groups and control group. When the cells were treated for 12 hours, 24 hours and 48 hours with FU ( 0.2μg/ml ), there was no significant statistic difference in 18F-FDG uptake rate of cells between all experimental groups and control group. But when the cells were treated for 12 hours, 24 hours and 48 hours with FU ( 2μg/ml and 20μg/ml ), there were significant statistic differences between all experimental groups and control group ( P values<0.01 ). ( 3 ) The results of biodistribution studies showed that when nude mice bearing colon cancer were treated at 2 h with FU, the 18F-FDG uptake of tumor started to decline; and when they were treated at 48 h, the 18F-FDG uptake of tumor reduced to minimum. ( 4 ) The results of 18F-FDG PET/CT imaging showed that the image of tumor of nude mice bearing tumor which were not treated was clear. ( 5 ) When the nude mice bearing tumor were treated after 6 days, there was significant statistic difference in the volume of tumor between experimental group and control group ( P=0.032 ). There was a growth trend of the tumor from before treatment to after FU treatment 8 d in experimental group, but compared to the volume of tumor with no treatment ( 0 d ), there was no significant statistic difference in the volume of tumor after FU treatment at 2 d, 4 d, 6 d and 8 d.2. Clinical study: In all 78 patients, recurrence and/or metastasis were confirmed in 54 patients and the remaining were not confirmed by histopathological diagnosis and/or long-term clinical follow-up data. There were 49 true positive and 21 true negative patients decided by PET/CT diagnosis. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of PET/CT and conventional imaging in diagnosis of recurrence and/or metastasis of postoperative colon cancer were 90.74%, 87.50%, 89.74%, 94.23%, 80.77% and 51.85%, 75.00%, 58.97%, 82.35%, 40.91%, respectively. The median survival, the 1- and 2-year cumulative survival rates were ( 28.00±7.11 ) months, 68.70% and 51.70%, respectively, in true positive group. There was only one patient who had died ( natural death ) in true negative group, so the median survival time was not available, but the 2-year cumulative survival rate could reach 90.00%. The range of all SUVmax values of 49 patients in true positive group was from 2.5 to 26.0 whose mean value and median were 8.16 and 6.70, respectively. Taking mean value 8.16 as a cutoff, the median survival, the 1- and 2-year cumulative survival rates were ( 28.00±8.78 ) months, 86.60% and 64.90%, respectively, in low SUV subgroup ( SUV<8.16 ) and ( 10.00±3.18 ) months, 46.30% and 34.80%, respectively, in high SUV subgroup ( SUV≥8.16 ) ( P=0.016 ). Taking median 6.70 as a cutoff, the median survival, the 1- and 2-year cumulative survival rates were ( 28.00±8.84 ) months, 85.40% and 62.10%, respectively, in low SUV subgroup ( SUV<6.70 ) and ( 16.00±5.60 ) months, 51.90% and 41.50%, respectively, in high SUV subgroup ( SUV≥6.7 ) ( P=0.066 ).Conclusions1. Preclinical research: When nude mice bearing colon cancer were treated with FU, the metabolic changes of tumors were significantly earlier than their morphological changes, and the glucose metabolism of tumor was restrained to the maximum extent at 48 h after treatment. The nude mice colon cancer subcutaneous models which were established successfully could be used for selecting new drugs for the treatment of colon cancer and optimizing treatment programs in vivo.2. Clinical study: 18F-FDG PET/CT for monitoring recurrence and/or metastasis in patients of postoperative colon cancer has much higher sensitivity and accuracy than conventional imaging. Taking mean value of SUVmax 8.16 as a cutoff plays an important role in prognosis of clinical outcomes for patients of postoperative colon cancer with recurrence and/or metastasis. |
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