PET／CT在评价及观察大鼠肺癌放疗效果中的应用

目的观察Wistar大鼠肺癌放疗后不同时期的PET／CT表现，观察和评价大鼠肺癌放疗疗效的时间点。方法将30只近交系Wistar大鼠（鼠龄6～8周，体质量180～280g，均为雌性普通级）制作成Lewis肺癌的模型鼠，肿瘤模型建立4—6周后当肿瘤长到最大径1．5～2．0cm时，对大鼠进行^18F-脱氧葡萄糖（FDG）PET／CT显像；显像后对大鼠进行肿瘤局部单次放疗，放疗剂量为5Gy。放疗后第3天和第1、第2、第3、第4周末再对大鼠进行PET／CT显像，观察放疗的疗效，从而评价疗效观察的时间点。而后取一部分肿瘤组织制成免疫组织化学切片，观察葡萄糖转运蛋白1（Glut1）的表达。一部分肿瘤组织被制成病理切片，经HE染色，观察光学显微镜下肿瘤细胞的坏死及萎缩情况。统计学处理采用SPSS11．0软件。多组样本均数之间比较采用单因素方差分析，标准摄取值（SUV）与Glut1表达行等级相关分析。结果随着放疗后时间的延长，^18F-FDG的摄取逐渐减少，代谢活性逐渐减低，SUV放疗前为1．28±0．31，放疗后第3天为1．00±0．23，放疗后第4周下降到0．18±0．10。放疗后各不同时间点肿瘤的平均SUV与放疗前的差异具有统计学意义（F=15．126，P〈0．05）。免疫组织化学结果：Glut1表达阳性的染色主要位于胞膜和胞质，随着放疗后观察时间的延长，肿瘤组织的Glut1表达逐渐减低，Glut1表达的平均吸光度（A）值放疗前为0．2558±0．03，放疗后第3天为0．2320±0．01，放疗后第4周为0．1320±0．04。肿瘤平均SUV与Glut1表达呈正相关（等级相关系数L=0．97，P〈0．01）。病理检查结果：随着放疗后观察时间的延长，肿瘤细胞萎缩、碎裂及坏死逐渐增多。结论PET／CT能于Wistar大鼠肺癌放疗后早期（第3天）观察到治疗效果，到第4周疗效显示最佳。

The effect of radiotherapy on rat pulmonary tumor model with PET/CT

Objective The aim of this study was to understand the role of PET/CT in monitoring the therapeutic effect of radiotherapy (RT) on lung cancer with Wistar rats. Methods Thirty Wistar in-bred strain rats (6-8 weeks, weighed 180-280 g, female, ordinary) were made into Lewis pulmonary tumor model rats. 18F-fluorodeoxyglucose (FDG) PET/CT was performed when tumor reached 1.5-2.0 cm in greatest diameter (4-6 weeks) as a baseline. In order to get the optimal time point of PET/CT for moni-toring RT effect in rat cancer model, PET/CT was performed at the 3rd day, 1st, 2nd, 3rd, and 4th week after giving single dose of 5 Gy to each rat. Standardized uptake values (SUV) from FDG PET were measured and rats were sacrificed at different time point for validation. Besides, the expressions of glucose transport1 (Glut1) in tumor tissue were studied using immunohistochemistry. The level of tumor cell apoptosis, degra-dation, and necrosis were observed. SPSS 11.0 software was used for data analyses. Results A negative correlation of SUV uptake and time after RT and negative correlation of Glut1 expression and time after RT were observed in rat tumors, respectively. Positive correlation of SUV uptake and Glut1 expression in rat tumors was observed (Spearman rank correlation test, rs = 0.97, P < 0.01). Before RT, the SUV in rat tumor was 1.28 ± 0.31 and was decrease to 1. 00 ± 0.23 at the 3rd day and 0.18 ± 0. 10 at the 4th week after RT (F=15. 126, P<0.05). Before RT, the Glut1 in rat tumor was 0.2558 ±0.03 and was decrease to 0. 2320 ± 0. 01 at the 3rd day and 0. 1320±0.04 at the 4th week after RT. The amounts of tumor cell apopto-sis, degradation, and necrosis increased with time after RT. Conclusion Though FDG PET could monitor the therapeutic effect at the 3rd day after giving single dose of RT to rat lung tumor model, the optimal time was the the 4th week after treatment.