The Clinical Application Value Of ~18 F-FLT PET/CT Imaging In Radiation Oncology

Part I The experimental study of evaluating the early effect of radiotherapy by uptake of ¹⁸F-FLT in human pancreatic carcinoma cell PaTu 8988Objective To evaluate the early effect of radiotherapy by uptake of ¹⁸F-FLT in human pancreatic carcinoma cell PaTu 8988. Methods The human pancreatic carcinoma cells PaTu 8988 were exposed to a single fraction ofγ-ray radiation of 0Gy, 2Gy, 4Gy or 8Gy, respectively. The OD values were detected by MTT at 24 hours and 48 hours after irradiation, and the cell inhibition rates were calculated. The uptakes of ¹⁸F-FLT were measured at 24 hours and 48 hours after irradiation, and the ¹⁸F-FLT uptake inhibition rates were calculated. Results At 24 hours after irradiation, the differences of OD values between groups of various dose were not significant （P>0.05）. At 48 hours after irradiation, the cell inhibition rates were （9.28±11.92）%, （21.03±3.37）% and （32.96±3.77）% （P<0.01）, respectively. At 24 hours and 48 hours after irradiation, the differences of ¹⁸F-FLT uptakes between groups of various dose were significant （P<0.05）. At 24 hours after irradiation, the ¹⁸F-FLT uptake inhibition rates were （6.99±11.93）%, （11.77±7.35）% and （25.57±7.61）%, respectively. At 48 hours after irradiation, the ¹⁸F-FLT uptake inhibition rates were （14.69±4.43）%, （17.71±6.08）% and （40.81±7.61）%, respectively. The ¹⁸F-FLT uptakes decreased with the increasing dose ofγ-ray. At 48 hours after irradiation, the cell inhibition rate was positively correlated with the ¹⁸F-FLT uptake inhibition rate （r=0.782,P<0.01）. Conclusion The uptakes of ¹⁸F-FLT with human pancreatic carcinoma cells PaTu 8988 decreased at 24h after irradiation. Response to radiotherapy could be predicted early by ¹⁸F-FLT PET scans. Part II The preliminary clinical study on different tumors with ¹⁸F-FLT PET/CT imagingObjective To evaluate the usefulness of ¹⁸F-FLT positron emission tomography （PET）/computed tomography （CT） for the detection of various carcinomas. Methods Thirty-one patients （23 male and 8 female） with histologically proven advanced carcinoma and one patient with pneumonia underwent whole-body ¹⁸F-FLT PET/CT. The thirty-one patients with advanced carcinoma included 13 patients of nasopharyngeal carcinoma （1 with undifferentiated carcinoma, 1 with medium differentiated squamous-cell carcinoma and 11 wih low differentiated squamous-cell carcinoma）, 9 patients of lung carcinoma （including 1 small cell lung cancer）, 6 patients of malignant lymphoma （including 4 with Hodgkin’s lymphoma and 2 with non-Hodgkin lymphoma）, 2 patients of laryngeal carcinoma and 1 of renal pelvic carcinoma. Maximum and mean standardized uptake values （SUVmax and SUVmean） for ¹⁸F-FLT were calculated using circular ROIs in the tumor and metastasis site to investigate how the SUVmax and SUVmean values were correlated with the type, pathology and stage of tumors and software SPSS was used for one-way analysis of the variance between groups or paired t-test. Results ¹⁸F-FLT PET/CT scanning on The thirty-one patients of advanced carcinoma provided high-quality images that uncovered 100 lesions clearly （including the primary tumors or metastasis sites）, from which the SUVmax and SUVmean of ¹⁸F-FLT were determined as 5.20±2.79 and 4.35±2.38, respectively ; while, ¹⁸F-FLT uptake for the patient of pneumonia was very low with SUVmax and SUVmean only 0.67 and 0.61, respectively. The SUVmax and SUVmean of lymph node metastasis in lung carcinoma were remarkably lower than those of primary tumors or metastatic legions （P<0.05）. the SUV values of different pathologies in the nasopharyngeal carcinomas varied not very much （P>0.05）. Both SUVmax and SUVmean of lymph node metastasis in low differentiated squamous cell lung cancer were notably lower than that of in low differentiated adenocacinoma and low differentiated squamous cell carcinoma of pulmonary lesions （P<0.05）. Both SUVmax and SUVmean of Hodgkin’s lymphoma were higher than that of non-Hodgkin lymphoma （P<0.05）. Conclusion The average SUVmax of Primary and metastatic lesions reached 5.20 with ¹⁸F-FLT PET/CT imaging. Being capable of showing the primary lesions and metastasis lesions of nasopharyngeal carcinoma, lung carcinoma, malignant lymphoma, laryngeal carcinoma and renal pelvic carcinoma, ¹⁸F-FLT PET/CT imaging is a technology of notable clinical value.PartⅢThe clinical application value of ¹⁸F-FLT PET/CT in the staging and treatment of carcimoma as compared with CT aloneObjective A comparative study on PET/CT fusion imaging and CT scan to explore the clinical application value of positron emission tomography-computed tomography using ¹⁸F-FLT both in the staging and treatment of carcinoma. Methods Staging of TNM for a total of 23 patients with carcinoma confirmed by pathological detection was assessed with both ¹⁸F-FLT PET/CT and CT alone. By observing the difference between the two staging methods, the treatment strategy of carcinoma can be adjusted according to the result of ¹⁸F-FLT PET/CT and clinical data. The research data were analyzed by SAS 9.1.0 software. Results 1. In accordance with the UICC TNM staging, the TNM defined by CT was altered by ¹⁸F-FLT PET/CT in 4 cases of 23 cases. There was no significant difference between PET/CT and CT in assessing the TNM staging（p>0.05）. Compared with CT staging, 2 cases were upstaged and 2 cases were downstaged by PET/CT. T staging in 4 cases was changed with PET/CT fusion images, in 1 case was upstaged and in 3 cases was downstaged. N staging was changed in 3 cases, 1 case was upstaged and 2 cases were downstaged. M staging was changed in only one case considered the lower right lung metastasis of recurrent laryngeal cancer by PET / CT fusion images, PET / CT showed high uptake of the lower right solitary pulmonary nodules, but follow-up data were eventually proven to be false positive. 2. The total change in TNM staging was evaluated in 4 cases which led to the change of treatment strategy in 3 cases. In one case of lung cancer the original plan of postoperative radiotherapy and chemotherapy were changed to long-term clinical observations, and maybe to avoid overtreatment. In 1 case of undifferentiated nasopharyngeal carcinoma , the dose of cervical lymph node was decreased by N stage from the N2 down to N0. 1 case of nasopharyngeal carcinoma ¹⁸F-FLT PET/CT showed parasellar brain involvement （T4） and the dose of the skull base was increased. Another 1 case of locally advanced （T4） with recurrent laryngeal carcinoma which ¹⁸F-FLT PET/CT fusion images showed solitary pulmonary metastasis of the lower right lung, but by comparing before and after three months of the PET / CT scans to exclude pulmonary metastases, maintained the original plan to the local radical IMRT. Conclusion Compared with CT alone, ¹⁸F-FLT PET / CT fusion imaging allowed more accurate staging. The better treatment can be received by the patients with carcinoma by optimizing the treatment strategy with ¹⁸F-FLT PET/CT imaging.PartⅣThe application value of ¹⁸F-FLT PET/CT fusion imaging in delineation of the gross tumor volume and evaluation of three-dimensional conformal radiotherapy plan in carcinomaObjective To investigate the influence of two outlining methods on delineation of gross tumor volume （GTVCT and GTVPET/CT） and the evaluation of radiotherapy plan by developing 3D-CRT plan based on the 3D treatment planning system with the two GTVs. Methods The gross tumor volume （GTV） of primary malignant lesions of 24 patients were delineated respectively on CT images and ¹⁸F-FLT PET/CT fusion images （taken the signal-to-background ratio of 40% as the threshold） to compare the difference between GTVCT and GTVPET/CT. 3D-CRT plans were developed as required respectively using GTVCT and GTVPET/CT acquired by two outlining methods, and the radiotherapy plans were evaluated in accordance with the dose distribution standard, in which 95% GTV should be included in 95% isodosecurve. Software SAS 9.1 was applied for the statistical analysis of the research data. Results 1. The GTVCT and GTVPET/CT spatial forms and volumes were varied in all 24 patients. Taking GTVPET/CT for reference, three correlations existed in GTV spatial form, i.e., inclusion （12 cases）, be-included （5 cases） and cross-relation （7 cases）. The average GTVCT and GTVPET/CT were respectively 52.21cm3 and 40.88cm3, which were no statistically significant difference （P>0.05）. GTVPET/CT was smaller than GTVCT in 17 cases with the average reduction of 20.11cm3, and GTVPET/CT was larger than GTVCT in 7 cases with the average enlargement of 9.93 cm3. 2. When the radiotherapy plans based on GTVPET/CT were evaluated with the optimized 3D-CRT plans of GTVCT, The target dose distribution requirements were not reached in 3 cases of total 24 patients and were achieved in the other 21 patients. However, when the optimized radiotherapy plans of GTVPET / CT were used to assess the dose distribution of GTVCT, only 50% （12/24） met the requirement of the standard treatment program. Conclusion ¹⁸F-FLT PET/CT fusion imaging changed the spatial form and volume in CT and provided the possibility to adjust and optimize the three-dimensional conformal radiotherapy plan.Part V The clinical study on the application of ¹⁸F-FLT imaging in predicting the carcinoma response to radiotherapyObjective To investigate the clinical value of using ¹⁸F-FLT PET/CT imaging in the early detection of the effect of radiotherapy based on the change of SUV value before and after treatment （△SUV）. Methods Nineteen patients with malignant tumor before three-dimensional conformal radiotherapy performed ¹⁸F-FLT PET/CT imaging. Twice ¹⁸F-FLT PET/CT imaging were performed before and 24 hours after 2Gy radiotherapy on thirteen patients （13/19）, including 9 with nasopharyngeal carcinoma, 1 with lung carcinoma, 1 with lymphoma, 1 of laryngeal carcinoma and 1 of renal pelvic carcinoma. SUVmax, SUVmean, and the percent changes in SUVmax and SUVmean （△SUVmax and△SUVmean） for ¹⁸F-FLT were calculated. The correlation between the SUV values shown by ¹⁸F-FLT PET/CT imaging with the response of the therapy was studied. So was the correlation between the value of△SUVmax before and after 2Gy radiotherapy and the response. Results The nineteen patients were divided into three groups, namely, 11 patients of Complete Response （CR）, 2 patients of Stable Disease （SD） and 6 of Progressive Disease （PD） based on the follow-up results, which turned out that the SUVmax and SUVmean values for ¹⁸F-FLT images of the CR group did not vary significantly from those of the PD group （P>0.05）. The thirteen patients who performed twice ¹⁸F-FLT PET/CT imaging were so divided as 7 patients of CR, 1 patient of SD and 5 of PD, where, the△SUVmax and△SUVmean for ¹⁸F-FLT images of the CR group were higher than SD and PD （P<0.05）. The SUVmax and SUVmean of the 9 patients with nasopharyngeal carcinoma were 6.54±3.27 and 5.52±2.75 before therapy, which became 4.43±2.21 and 3.76±1.84 24 hours after 2Gy therapy, with△SUVmax and△SUVmean being （31.25±16.18）% and （30.75±15.92）% respectively. According to follow-up results, the nine patients with nasopharyngeal carcinoma were divided into three groups, 6 in the CR group, 1 in the SD group and 2 in the PD group, where, the values of△SUVmax and△SUVmean in the CR group were significantly higher than both the SD and the PD groups （P<0.05）. Conclusion For the patients in the CR group, the SUV value decreased evidently after 2Gy radiotherapy. It can be concluded that it may help predict the carcinoma response to radiotherapy by finding out the△SUV between the SUV values before and after the ¹⁸F-FLT PET/CT imaging.