Pretreatment 18F-FAZA PET predicts success of hypoxia-directed radiochemotherapy using tirapazamine
Pretreatment 18F-FAZA PET predicts success of hypoxia-directed radiochemotherapy using tirapazamine
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DOI：
10.2967/jnumed.106.038570
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发表时间：
2007-06-01
影响因子：
9.3
通讯作者：
Piert, Morand
中科院分区：
文献类型：
--
作者：
Beck, Roswitha;Roeper, Barbara;Piert, Morand
我们评估了PET的预测价值，使用缺氧示踪剂F-18-氟唑霉素阿拉伯糖苷（F-18-FAZA）与替拉扎明（一种针对缺氧细胞的特异性细胞毒素）联合放疗的成功率。研究方法：对荷EMT 6肿瘤的裸鼠进行成像，然后将小鼠分配到4组：放化疗（RCT：4天内8次4.5戈伊联合替拉扎明，14 mg/kg）、单独放疗（RT）、单独化疗（替拉扎明）（CHT）或对照组。通过几种肿瘤生长试验评估治疗成功，包括70至500 LL的肿瘤生长时间和绝对生长延迟（aGD）。中位预处理F-18-FAZA肿瘤与背景比用作“低氧”和“常氧”肿瘤之间的中间值。结果如下：与常氧对照肿瘤（生长时间从70 μ L到500 μ L，15.6天）相比，缺氧对照肿瘤的平均肿瘤生长显着加速（生长时间从70 μ L到500 μ L，11.0天）。而RT延迟肿瘤的生长，无论缺氧水平，添加剂有益的治疗效果的替拉扎明RT观察到只有在缺氧肿瘤（aGD，12.9天），但不是在常氧肿瘤（aGD，6.0天）。结论：这项研究提供了令人信服的证据，缺氧成像使用F-18-FAZA PET能够预测成功的RCT荷瘤小鼠使用缺氧激活的化疗剂替拉扎明。因此，治疗前F-18-FAZA PET为涉及放射的肿瘤治疗的个体化提供了一种方法。这些数据表明，通过将低氧导向治疗保留给具有高F-18-FAZA摄取的肿瘤，可以提高治疗率，因为替拉扎明的治疗效果似乎仅限于低氧肿瘤。
We evaluated the predictive value of PET using the hypoxia tracer F-18-fluoroazomycin arabinoside (F-18-FAZA) for success of radiotherapy in combination with tirapazamine, a specific cytotoxin for hypoxic cells. Methods: Imaging was performed on EMT6 tumor-bearing nude mice before allocating mice into 4 groups: radiochemotherapy (RCT: 8 fractions of 4.5 Gy within 4 d combined with tirapazamine, 14 mg/kg), radiotherapy alone (RT), chemotherapy alone (tirapazamine) (CHT), or control. Treatment success was assessed by several tumor growth assays, including tumor growth time from 70 to 500 LL and absolute growth delay (aGD). The median pretreatment F-18-FAZA tumor-to-background ratio served as a discriminator between "hypoxic" and "normoxic" tumors. Results: The mean tumor growth was significantly accelerated in hypoxic control tumors (growth time from 70 to 500 mu L, 11.0 d) compared with normoxic control tumors (growth time from 70 to 500 mu L, 15.6 d). Whereas RT delayed tumor growth regardless of the level of hypoxia, an additive beneficial therapeutic effect of tirapazamine to RT was observed only in hypoxic tumors (aGD, 12.9 d) but not in normoxic tumors (aGD, 6.0 d). Conclusion: This study provides compelling evidence that hypoxia imaging using F-18-FAZA PET is able to predict the success of RCT of tumor-bearing mice using the hypoxia-activated chemotherapeutic agent tirapazamine. Pretreatment F-18-FAZA PET, therefore, offers a way for the individualization of tumor treatment involving radiation. The data suggest that by reserving hypoxia-directed therapy to tumors with high F-18-FAZA uptake, improvement of the therapeutic ratio is possible, as the therapeutic effect of tirapazamine seems to be restricted to hypoxic tumors.