Wang Hui, Zhang Jinming, Tian Jiahe, Qu Baolin, Li Tianran, Chen Yingmao, Liu Jian, Wang Shan
Nuclear Medicine Department, General Hospital of the Chinese People's Liberation Army and Military Medical Postgraduate College, Beijing, China.
J Nucl Med. 2009 Nov;50(11):1857-64. doi: 10.2967/jnumed.109.064238. Epub 2009 Oct 16.
(18)F-FDG and 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) have been proven useful in diagnosing and staging many types of cancer but with emphasis on different aspects of tumor biology. The aim of the current study was to evaluate whether (18)F-FDG and (18)F-FLT can be used complementarily in monitoring the biologic characteristics of colorectal cancer (CRC).
Human CRC cell lines SW480 and SW620 of the same genetic origin but different metastatic potential were cultured and implanted into nude mice to create CRC models. Uptake of (18)F-FDG and (18)F-FLT in SW480 and SW620 cells in vitro was assessed after incubation with radiotracers for 0, 30, 60, 90, and 120 min. In vivo imaging of SW480 and SW620 tumor-bearing mice was performed using small-animal PET/CT at 60 min after injection of each tracer. A region of interest was drawn over tumor and background to calculate the tumor-to-nontumor ratio (T/NT) using software on reconstructed images. Tumor growth rate, metastatic status, and survival time were assessed in tumor-bearing mice. The relationship between uptake of the tracers, metastatic capability, and tumor marker expression was evaluated using linear regression.
SW480 tumors grew more quickly than SW620 tumors (t = 3.332, P = 0.004). A higher incidence of lung and liver metastases was noted for SW480 than for SW620 (P = 0.023). Uptake in SW480 and SW620 cells was significantly different between (18)F-FDG and (18)F-FLT (t = 2.507, P = 0.021, vs. t = 3.497, P = 0.002). In the small-animal PET study, the T/NT of (18)F-FDG did not differ between SW480 and SW620 tumors (2.69 +/- 0.98 vs. 3.09 +/- 1.26, P = 0.524), but the T/NT of (18)F-FLT differed significantly between SW480 and SW620 tumors (3.65 +/- 0.51 vs. 2.22 +/- 0.42, P < 0.001). Heat shock protein 27 (HSP27) expression and integrin beta(3) expression were higher, whereas vascular endothelial growth factor receptor 2 (VEGFR2) expression and Ki67 expression were lower, in SW480 cells than in SW620 cells. For SW480, metastases in lung and liver correlated significantly with (18)F-FLT uptake in tumors (r = 0.763, P = 0.005) and with expression of HSP27 (r = 0.894, P = 0.008) and integrin beta(3) (r = 0.635, P = 0.088). A correlation was also found between (18)F-FLT uptake and expression of HSP27 (r = 0.924, P = 0.004) and integrin beta(3) (r = 0.813, P = 0.025). No correlation was found between (18)F-FDG uptake in tumors and metastasis in lung and liver (r = -0.111, P = 0.388). However, there was a significantly negative correlation between (18)F-FDG uptake and the survival time of tumor-bearing mice (r = -0.500, P = 0.017), to which (18)F-FLT did not relate (r = 0.262, P = 0.182).
High uptake of (18)F-FDG and (18)F-FLT may reflect poorer survival and a higher metastatic potential for CRC in mice. Combining (18)F-FDG with (18)F-FLT PET would be helpful in better predicting the biologic behavior of CRC.
（18）F-FDG和3'-脱氧-3'-（18）F-氟胸苷（（18）F-FLT）已被证明在多种癌症的诊断和分期中有用，但侧重于肿瘤生物学的不同方面。本研究的目的是评估（18）F-FDG和（18）F-FLT是否可互补用于监测结直肠癌（CRC）的生物学特性。
培养具有相同遗传起源但转移潜能不同的人CRC细胞系SW480和SW620，并将其植入裸鼠体内以建立CRC模型。在与放射性示踪剂孵育0、30、60、90和120分钟后，评估SW480和SW620细胞中（18）F-FDG和（18）F-FLT的摄取情况。在注射每种示踪剂后60分钟，使用小动物PET/CT对荷SW480和SW620肿瘤的小鼠进行体内成像。在重建图像上使用软件在肿瘤和背景上绘制感兴趣区域，以计算肿瘤与非肿瘤比值（T/NT）。评估荷瘤小鼠的肿瘤生长速率、转移状态和生存时间。使用线性回归评估示踪剂摄取、转移能力和肿瘤标志物表达之间的关系。
SW480肿瘤比SW620肿瘤生长更快（t = 3.332，P = 0.004）。SW480的肺和肝转移发生率高于SW620（P = 0.023）。（18）F-FDG和（18）F-FLT在SW480和SW620细胞中的摄取存在显著差异（t = 2.507，P = 0.021，对比t = 3.497，P = 0.002）。在小动物PET研究中，（18）F-FDG的T/NT在SW480和SW620肿瘤之间无差异（2.69±0.98对比3.09±1.26，P = 0.524），但（18）F-FLT的T/NT在SW480和SW620肿瘤之间存在显著差异（3.65±0.51对比2.22±0.42，P < 0.001）。SW480细胞中的热休克蛋白27（HSP27）表达和整合素β3表达较高，而血管内皮生长因子受体2（VEGFR2）表达和Ki67表达低于SW620细胞。对于SW480，肺和肝转移与肿瘤中（18）F-FLT摄取显著相关（r = 0.763，P = 0.005），与HSP27表达（r = 0.89,4，P = 0.008）和整合素β3（r = 0.635，P = 0.088）也显著相关。还发现（18）F-FLT摄取与HSP27表达（r = 0.924，P = 0.004）和整合素β3（r = 0.813，P = 0.025）之间存在相关性。肿瘤中（18）F-FDG摄取与肺和肝转移之间无相关性（r = -0.111，P = 0.388）。然而，（18）F-FDG摄取与荷瘤小鼠的生存时间之间存在显著负相关（r = -0.500，P = 0.017），（18）F-FLT与之无关（r = 0.262，P = 0.182）。
（18）F-FDG和（18）F-FLT的高摄取可能反映小鼠CRC的较差生存和较高转移潜能。将（18）F-FDG与（18）F-FLT PET联合使用有助于更好地预测CRC的生物学行为。
