Animal And Clinical Studies Of ¹⁸f-fdg Pet-ct In Early Assessment Of Radiotherapy Efficacy Of Nasopharyngeal Carcinoma And The Correlation Analysis Of Ki67 Expression

[Objectives] 1. To investigate the effect of ¹⁸F-FDG PET-CT imaging in early assessment of radiotherapy efficacy of transplanted nasopharyngeal carcinoma in nude mice and to explore the appropriate imaging time. 2. To research the change of Ki67 expression in different time of radiotherapy of transplanted nasopharyngeal carcinoma in nude mice. 3. To investigate the characteristics of imaging of ¹⁸F-FDG PET-CT in different time of radiotherapy and to explore the feasibility and value of ¹⁸F-FDG PET-CT early imaging in nasopharyngeal carcinoma patients who received radiotherapy. 4.To investigate the characteristics of dual-time imaging in radiotherapy of nasopharyngeal carcinoma. 5. To explore the relation between the expression of Ki67 before radiotherapy of nasopharyngeal carcinoma and the change of SUVmax during the period of radiotherapy.[Materials/Methods] 1. 15 nude mice transplanted nasopharyngeal carcinoma xenografts were randomly divided into control group, 6Gy radiotherapy group and 12Gy radiotherapy group. 6Gy radiotherapy group and 12Gy radiotherapy group received ¹⁸F-FDG PET-CT imaging 1st ,2nd ,4th and 6th day respectively after radiotherapy. The largest cross-sectional area of tumor and T / NT ratios were measured, and all the mice was executed for pathological examination after the last imaging.2. The expression of Ki67 in xenografts of different groups was detected by immunohistochemistry, and their changes at different stages of radiotherapy as well as T / NT relationship were analyzed.3. 12 Untreated patients with nasopharyngeal carcinoma received ¹⁸F-FDG PET-CT imaging respectively for measuring SUVmax before radiotherapy, during radiotherapy when 50Gy was given and 1 week after radiotherapy. The SUVmax in different tumor stage, different tumor regression rates were compared, and the SUVmax in patients who were in the first week after radiotherapy and in who were in the fifth month after radiotherapy and detected relapse-free by PET-CT imaging.4. 12 untreated patients with nasopharyngeal carcinoma received ¹⁸F-FDG PET-CT imaging and delayed imaging respectively for measuring SUVmax and comparative analyzing before radiotherapy during radiotherapy when 50Gy was given and 1 week after radiotherapy.5. The expression of Ki67 protein in paraffin blocks of 12 NPC patients was detected by immunohistochemical method before radiotherapy and analyze the correlation with SUVmax in different stages of radiotherapy.[Results] 1①The largest tumor cross-section of xenografts was reduced by 19.31%±5.19% in the 6th day after radiotherapy, and the result had significant difference compared with that before radiotherapy (t = 5.684, P <0.01);②The T / NT ratios continuously decreased and reduce to 0.70±0.12 6 days after radiotherapy, and the result had significant difference compared with those before radiotherapy , during radiotherapy when 6Gy,12Gy were administered respectively (P <0.01).2①nasopharyngeal carcinoma tumor Ki67 antigen expression increased with the radiation dose significantly reduced Ki67 expression between different groups were significantly different (F = 12.5, P <0.01): 12Gy radiotherapy group Ki67 expression was significantly lower than the control group (P < ; 0.01) and 6Gy radiotherapy group (P <0.01); 6Gy radiotherapy group the expression of Ki67 also lower than the control group there were statistically significant (P <0.01).②tumor during radiation therapy FDG uptake (T / NT) of the change and Ki67 expression was significantly correlated (correlation coefficient r = 0.732, P <0.01)3①There was positive correlation between SUVmax and the maximum cross-section of tumor (correlation coefficient r = 0.746, P <0.01);②SUVmax in patients with high stage (III + IV) were higher than those in patients with low stage (I + II) before radiotherapy, during radiotherapy when 50Gy was administered and 1 week after radiotherapy;③The SUVmax was 2.36±0.21 in patients whose tumor regression rate was≥90% during radiotherapy when 50Gy was given, and the counterpart was 3.45±1.07 in patients whose tumor regression rate was < 90%,and there was significant difference between the two parts.(t = 2.235, P <0.05) ;④week after radiotherapy the average SUVmax was 2.45±0.35, mean SUVmax radiotherapy negative control group was 2.49±0.57, that there is no statistical difference (t = 0.179, P> 0.05)4①The average SUVmax was 9.63±4.51 in early imaging before radiotherapy, and the average SUVmax in delayed imaging was 10.53±5.03, which was higher than that in early imaging by 8.63±7.83%, and there was significant statistical difference (t = 3.938, P <0.01) ;②The average SUVmax was3.00±0.98 in early imaging during radiotherapy when 50Gy was administered, and the average SUVmax in delayed imaging was 3.06±1.31, and there was no significant difference between the two results (t = 0.516, P> ; 0.05);③T he SUVmax in early imaging and delayed imaging 1 week after radiotherapy was 2.45±0.35, 2.34±0.35 respectively , and there was significant difference between the two numbers (t = 2.6, P < ; 0.05).5 There was no association between SUVmax and expression of Ki67 before radiotherapy(P> 0.05); The level of SUVmax in patients who had high expression Ki67 was significantly lower than that in patients with lower expression, and there was statistical difference (t = 2.235 , P <0.05).[Conclusions]: 1. The changes of FDG uptake levels in nasopharyngeal carcinoma xenografts after radiotherapy suggests that ¹⁸F-FDG PET-CT has the function of early assessing the radiotheraputic effects of nasopharyngeal carcinoma. 2. The FDG uptake in nasopharyngeal carcinoma xenografts was decreased significantly in the 6th day after radiotherapy, showing that the effect of inflammatory exudation on FDG uptake was reduced to a lower level, which may be the appropriate time to monitor the early radiotheraputic effects. 3. There was positive correlation between the changes of FDG uptake in xenografts and the changes in Ki67 expression during radiotherapy, implying that the reduction of tumor cell proliferation in the course of radiotherapy was one of the main factors of causing the reduction of FDG uptake.4. Nasopharyngeal carcinoma staging and tumor size are important factors in affecting the SUVmax before radiotherapy, and Ki67 expression has nothing to do with the SUVmax before radiotherapy. 5. ¹⁸F-FDG PET-CT examination in patients with nasopharyngeal carcinoma 1 week after radical radiotherapy line can correctly determine efficacy of radiotherapy. 6. dual-time imaging benefits early evaluation of radiotherapy. 7. The SUVmax reduced rapidly in patients whose Ki67 expression was high before radiotherapy, which is an important factor in affecting the changes of SUVmax during radiation therapy.