Hypoxia imaging with (18)F-FAZA PET/CT predicts radiotherapy response in esophageal adenocarcinoma xenografts.
Hypoxia imaging with (18)F-FAZA PET/CT predicts radiotherapy response in esophageal adenocarcinoma xenografts.
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DOI：
10.1186/s13014-018-0984-3
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发表时间：
2018-03-07
期刊：
影响因子：
--
通讯作者：
Pattyn P
中科院分区：
文献类型：
--
作者：
Melsens E;De Vlieghere E;Descamps B;Vanhove C;Kersemans K;De Vos F;Goethals I;Brans B;De Wever O;Ceelen W;Pattyn P
食管癌是一种侵袭性疾病，生存率很低。基于预测生物标志物的更适合患者的方法可以改善结果。我们的目的是通过在食管腺癌 (EAC) 小鼠模型中使用 18F-FAZA PET/CT 对肿瘤缺氧进行成像来预测放疗 (RT) 反应。此外，我们还研究了缺氧调节剂尼莫拉唑的体外和体内放射增敏作用。体外 MTS 细胞增殖测定（OACM5 1.C SC1，人 EAC 细胞系）在常氧和低氧 (< 1%) 条件下进行：对照 (100 μL PBS)、尼莫拉唑、有或没有尼莫拉唑的照射（5、10 或 20 Gy）。在体内，在裸鼠（OACM5 1.C SC1）中诱导皮下异种移植物。连续 5 天每天进行治疗：(A) 对照（腹膜内注射 600 µl NaCl 0.9% (IP)）（N = 5，n = 7），(B) 放疗（5 Gy/d）（N = 11，n = 20），(C) 组合（尼莫拉唑（200 mg/kg/d IP） RT 前 30 分钟）（N = 13，n = 21）。 N = 小鼠数量，n = 肿瘤数量。治疗前进行18F-FAZA PET/CT并计算肿瘤与背景(T/B)比率。计算相对肿瘤生长并对肿瘤切片进行组织学检查（缺氧、增殖）。治疗前 18F-FAZA PET/CT 的 T/B ≥ 3.59 可预测 RT 反应较差（敏感性 92.3%，特异性 71.4%）。与常氧肿瘤（T/B< 3.59）相比，放疗对缺氧肿瘤（T/B ≥ 3.59）的疗效较差（P = 0.0025）。在体外，尼莫拉唑预处理显着降低了缺氧放射抗性（P < 0.01），而在体内，尼莫拉唑增强了放疗抑制缺氧肿瘤区域癌细胞增殖的功效（Ki67，P = 0.064），但不影响肉眼可见的肿瘤生长。使用 18F-FAZA PET/CT 测量的肿瘤组织缺氧可预测 EAC 异种移植模型中的 RT 反应。尼莫拉唑的放射增敏作用值得怀疑，需要进一步研究。本文的在线版本 (10.1186/s13014-018-0984-3) 包含补充材料，可供授权用户使用。
Esophageal cancer is an aggressive disease with poor survival rates. A more patient-tailored approach based on predictive biomarkers could improve outcome. We aimed to predict radiotherapy (RT) response by imaging tumor hypoxia with 18F-FAZA PET/CT in an esophageal adenocarcinoma (EAC) mouse model. Additionally, we investigated the radiosensitizing effect of the hypoxia modifier nimorazole in vitro and in vivo. In vitro MTS cell proliferation assays (OACM5 1.C SC1, human EAC cell line) were performed under normoxic and hypoxic (< 1%) conditions: control (100 μL PBS), nimorazole, irradiation (5, 10 or 20 Gy) with or without nimorazole. In vivo, subcutaneous xenografts were induced in nude mice (OACM5 1.C SC1). Treatment was given daily for 5 consecutive days: (A) control (600 μl NaCl 0.9% intraperitoneally (IP)) (N = 5, n = 7), (B) RT (5 Gy/d) (N = 11, n = 20), (C) combination (nimorazole (200 mg/kg/d IP) 30 min before RT) (N = 13, n = 21). N = number of mice, n = number of tumors. 18F-FAZA PET/CT was performed before treatment and tumor to background (T/B) ratios were calculated. Relative tumor growth was calculated and tumor sections were examined histologically (hypoxia, proliferation). A T/B ≥ 3.59 on pre-treatment 18F-FAZA PET/CT was predictive for worse RT response (sensitivity 92.3%, specificity 71.4%). Radiation was less effective in hypoxic tumors (T/B ≥ 3.59) compared to normoxic tumors (T/B < 3.59) (P = 0.0025). In vitro, pre-treatment with nimorazole significantly decreased hypoxic radioresistance (P < 0.01) while in vivo, nimorazole enhanced the efficacy of RT to suppress cancer cell proliferation in hypoxic tumor areas (Ki67, P = 0.064), but did not affect macroscopic tumor growth. Tumor tissue hypoxia as measured with 18F-FAZA PET/CT is predictive for RT response in an EAC xenograft model. The radiosensitizing effect of nimorazole was questionable and requires further investigation. The online version of this article (10.1186/s13014-018-0984-3) contains supplementary material, which is available to authorized users.
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影响因子：
5.7
作者：
Saga T;Inubushi M;Koizumi M;Yoshikawa K;Zhang MR;Tanimoto K;Horiike A;Yanagitani N;Ohyanagi F;Nishio M
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影响因子：
5.7
作者：
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