大鼠C6胶质瘤放射治疗前后^18F—FDG摄取水平变化与多种生物学指标的相关性研究

目的探讨大鼠C6胶质瘤放疗前后^18F-FDG摄取水平变化及其与肿瘤细胞密度、Glut、细胞增殖及血管生成的关系。方法30只雄性荷C6胶质瘤SD大鼠按随机数字表法分为A、B和C3组，每组10只，均接种肿瘤细胞。2周后，A组行^18F-FDG PET／CT显像，B和C组分别于放疗后48h、1周行^18F-FDG PET／CT显像，计算肿瘤与对侧脊柱旁肌肉的SUVmax比值（TIM），观察放疗前后肿瘤TIM的变化。显像后处死大鼠，取出肿瘤组织，观察组织病理变化，并计数肿瘤细胞密度，免疫组织化学法测定肿瘤Ki67标记指数（Ki67 LI）及微血管密度（MVD），Western blot法检测Glut-1及VEGF的表达，采用单因素方差分析比较放疗前后T／M及各指标的变化，双变量相关分析评价T／M变化与各生物学指标间的相关性。结果（1）A、B、C3组T／M、肿瘤细胞密度、Ki67LI、MVD、Glut-1及VEGF水平总体比较组间差异均有统计学意义（F值依次为6．77，60．66，104．56，95．49，9．13和24．48，P均〈0．05）。两两比较示，B组T／M（9．23±4．56）、肿瘤细胞密度（672．70±92．98）及Ki67 LI（18．56±2．26）与A组（10．86±3．31，730．50±78．93，20．02±2．14）差异无统计学意义（P均〉0．05），C组（5．16±2．52，355．60±72．62，7．81±1．76）与A、B2组相比下降明显，差异均有统计学意义（P均〈0．05）；B组MVD（19．50±1．96）及Glut-1水平（0．20±0．09）较A组（17．90±2．02，0．15±0．04）差异无统计学意义（P均〉0．05），C组该两指标（8．40±1．84，0．07±0．06）显著下降，且与A、B2组间差异均有统计学意义（P均〈0．05）。B组肿瘤VEGF表达（0．42±0．13）与A组、C组（分别为0．17±0．04，0．16±0．09）相比显著增高，差异均有统计学意义（P均〈0．05）。（2）A、B组间T／M变化与肿瘤细胞密度变化呈明显正相关（r=0．81，P〈0．05）；A、C组间T／M变化与肿瘤细胞密度、Ki67 LI、MVD、Glut-1的变化呈正相关（r分别为0．83，0．71，0．68，0．62，P均〈0．05）。结论大鼠C6胶质瘤放疗后^18F—FDG摄取水平变化在放疗后48h仅与肿瘤细胞密度变化相关，而放疗后1周则能体现放疗引起的肿瘤多种生物学改变。

The correlations between 18F-FDG uptake and a variety of tumor biological indicators in C6 glioma rats with radiotherapy

Objective To study the relationship between 18F-FDG uptake and tumor cell density,glucose transporter expression,cellular proliferation and angiogenesis before and after radiotherapy in C6 glioma rats.Methods Thirty C6 glioma-bearing male SD rats were randomly divided into three groups:A,B and C ( 10 rats in each group).Two weeks later,18F-FDG PET/CT was performed in group A.In groups B and C,18 F-FDG PET/CT was performed at 48 h and 1 week after radiotherapy,respectively.The ratio of SUVmax of tumor to muscle (T/M) was calculated.HE staining,immunohistochemical staining and Western blot were used to measure tumor cell density,Ki67 labeling index ( LI),microvessel density ( MVD),Glut-1 and VEGF expression quantitatively.The one-way analysis of variance and bivariate correlation analysis were used to compare the changes of each indicator and evaluate the correlation between T/M and biological indicators,respectively.Results Significant differences of T/M,tumor cell density,Ki67 LI,MVD,Glut-1 and VEGF among groups A,B and C were observed ( F =6.77,60.66,104.56,95.49,9.13,24.48,respectively,all P ＜0.05).Least significant difference (LSD) test showed that there was no significant difference between group A and B in T/M,tumor cell density and Ki67 LI ( 10.86 ± 3.31,730.50 ± 78.93,20.02 ± 2.14 vs 9.23 ± 4.56,672.70 ± 92.98,18.56 ± 2.26).However,the indicators of group C (5.16 ± 2.52,355.60 ± 72.62,7.81 ± 1.76 ) were significantly decreased compared with those of groups A and B (all P ＜0.05 ).MVD and Glut-1 expression of group B increased slightly compared with those of group A ( 19.50 ± 1.96,0.20 ± 0.09 vs 17.90 ± 2.02,0.15 ± 0.04),but the difference was not statistically significant.Nevertheless,the two indicators were significantly decreased in group C ( 8.40 +1.84 and 0.07 ±0.06,P ＜0.05).VEGF expression in group B (0.42 ±0.13) was significantly higher than that in groups A and C (0.17 ±0.04 and 0.16 ± 0.09) ( both P ＜ 0.05 ).The changes of T/M were positively correlated with the changes of tumor cell density between groups A and B ( r =O.81,P ＜ 0.05 ).Changes of T/M were positively correlated with the changes of tumor cell density,Ki67 LI,MVD and Glut-1 between groups A and C (r =O.83,0.71,0.68,0.62,all P ＜ 0.05 ).Conclusions The changes of 18 F-FDG uptake in C6 glioma rats were only correlated to the changes of tumor cell density at 48 h after radiotherapy.However,the changes of 18F-FDG uptake closely correlate to the changes of a variety of biological indicators at 1 week post radiotherapy.