Beck Roswitha, Röper Barbara, Carlsen Janette Maria, Huisman Marc Cornelis, Lebschi Julia Aloisia, Andratschke Nicolaus, Picchio Maria, Souvatzoglou Michael, Machulla Hans-Jürgen, Piert Morand
Clinic for Nuclear Medicine, Technische Universität München, Munich, Germany.
J Nucl Med. 2007 Jun;48(6):973-80. doi: 10.2967/jnumed.106.038570.
We evaluated the predictive value of PET using the hypoxia tracer (18)F-fluoroazomycin arabinoside ((18)F-FAZA) for success of radiotherapy in combination with tirapazamine, a specific cytotoxin for hypoxic cells.
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 microL and absolute growth delay (aGD). The median pretreatment (18)F-FAZA tumor-to-background ratio served as a discriminator between "hypoxic" and "normoxic" tumors.
The mean tumor growth was significantly accelerated in hypoxic control tumors (growth time from 70 to 500 microL, 11.0 d) compared with normoxic control tumors (growth time from 70 to 500 microL, 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).
This study provides compelling evidence that hypoxia imaging using (18)F-FAZA PET is able to predict the success of RCT of tumor-bearing mice using the hypoxia-activated chemotherapeutic agent tirapazamine. Pretreatment (18)F-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 (18)F-FAZA uptake, improvement of the therapeutic ratio is possible, as the therapeutic effect of tirapazamine seems to be restricted to hypoxic tumors.
我们评估了使用缺氧示踪剂（18）F-氟阿糖胞苷（（18）F-FAZA）的PET对放疗联合替拉扎明（一种针对缺氧细胞的特异性细胞毒素）治疗成功的预测价值。
在将EMT6荷瘤裸鼠分为4组之前进行成像：放化疗（RCT：4天内8次，每次4.5 Gy，联合替拉扎明，14 mg/kg）、单纯放疗（RT）、单纯化疗（替拉扎明）（CHT）或对照组。通过多种肿瘤生长测定评估治疗效果，包括从70到500微升的肿瘤生长时间和绝对生长延迟（aGD）。预处理时（18）F-FAZA肿瘤与背景比值的中位数用作“缺氧”和“正常氧合”肿瘤之间的区分指标。
与正常氧合对照肿瘤（从70到500微升的生长时间，15.6天）相比，缺氧对照肿瘤的平均肿瘤生长明显加速（从70到500微升的生长时间，11.0天）。虽然放疗无论缺氧程度如何都能延迟肿瘤生长，但仅在缺氧肿瘤中观察到替拉扎明对放疗有额外的有益治疗效果（aGD，12.9天），而在正常氧合肿瘤中未观察到（aGD，6.0天）。
本研究提供了令人信服的证据，表明使用（18）F-FAZA PET进行缺氧成像能够预测荷瘤小鼠使用缺氧激活化疗药物替拉扎明的放化疗治疗成功。因此，预处理（18）F-FAZA PET为涉及放疗的肿瘤个体化治疗提供了一种方法。数据表明，通过将缺氧导向治疗保留给（18）F-FAZA摄取高的肿瘤，有可能提高治疗比，因为替拉扎明的治疗效果似乎仅限于缺氧肿瘤。
