Postema Ernst J, McEwan Alexander J B, Riauka Terence A, Kumar Piyush, Richmond Dacia A, Abrams Douglas N, Wiebe Leonard I
Department of Oncology, University of Alberta, 11560 University Avenue, Edmonton, Alberta, T6G 1Z2, Canada.
Eur J Nucl Med Mol Imaging. 2009 Oct;36(10):1565-73. doi: 10.1007/s00259-009-1154-5. Epub 2009 May 9.
Tumour hypoxia is thought to play a significant role in the outcome of solid tumour therapy. Positron emission tomography (PET) is the best-validated noninvasive technique able to demonstrate the presence of hypoxia in vivo. The locally developed PET tracer for imaging hypoxia, 1-alpha-D: -(5-deoxy-5-[(18)F]-fluoroarabinofuranosyl)-2-nitroimidazole ((18)F-FAZA), has been shown to accumulate in experimental models of tumour hypoxia and to clear rapidly from the circulation and nonhypoxic tissues. The safety and general biodistribution patterns of this radiopharmaceutical in patients with squamous cell carcinoma of the head and neck (HNSCC), small-cell lung cancer (SCLC) or non-small-cell lung cancer (NSCLC), malignant lymphoma, and high-grade gliomas, were demonstrated in this study.
Patients with known primary or suspected metastatic HNSCC, SCLC or NSCLC, malignant lymphoma or high-grade gliomas were dosed with 5.2 MBq/kg of (18)F-FAZA, then scanned 2-3 h after injection using a PET or PET/CT scanner. Images were interpreted by three experienced nuclear medicine physicians. The location and relative uptake scores (graded 0 to 4) of normal and abnormal (18)F-FAZA biodistribution patterns, the calculated tumour-to-background (T/B) ratio, and the maximum standardized uptake value were recorded.
Included in the study were 50 patients (32 men, 18 women). All seven patients with high-grade gliomas showed very high uptake of (18)F-FAZA in the primary tumour. In six out of nine patients with HNSCC, clear uptake of (18)F-FAZA was observed in the primary tumour and/or the lymph nodes in the neck. Of the 21 lymphoma patients (15 with non-Hodgkin's lymphoma and 6 with Hodgkin's disease), 3 demonstrated moderate lymphoma-related uptake. Of the 13 lung cancer patients (12 NSCLC, 1 SCLC), 7 had increased (18)F-FAZA uptake in the primary lung tumour. No side effects of the administration of (18)F-FAZA were observed.
This study suggests that (18)F-FAZA may be a very useful radiopharmaceutical to image hypoxia in the tumour types selected. Especially the high uptake by gliomas was encouraging. Given the good imaging properties, including acceptable T/B ratios in the tumour categories studied, (18)F-FAZA could be considered as a very promising agent for assessing the hypoxic fraction of these tumour types.
肿瘤缺氧被认为在实体瘤治疗结果中起重要作用。正电子发射断层扫描（PET）是能够在体内证实缺氧存在的最佳验证的非侵入性技术。本地研发的用于缺氧成像的PET示踪剂1-α-D:-(5-脱氧-5-[(18)F]-氟阿拉伯呋喃糖基)-2-硝基咪唑((18)F-FAZA)，已显示在肿瘤缺氧实验模型中蓄积，并能迅速从循环系统和非缺氧组织中清除。本研究展示了这种放射性药物在头颈部鳞状细胞癌（HNSCC）、小细胞肺癌（SCLC）或非小细胞肺癌（NSCLC）、恶性淋巴瘤和高级别胶质瘤患者中的安全性和一般生物分布模式。
已知患有原发性或疑似转移性HNSCC、SCLC或NSCLC、恶性淋巴瘤或高级别胶质瘤的患者，静脉注射5.2 MBq/kg的(18)F-FAZA，然后在注射后2 - 3小时使用PET或PET/CT扫描仪进行扫描。图像由三位经验丰富的核医学医师解读。记录正常和异常(18)F-FAZA生物分布模式的位置和相对摄取分数（0至4级）、计算的肿瘤与本底（T/B）比值以及最大标准化摄取值。
本研究纳入了50例患者（32例男性，18例女性）。所有7例高级别胶质瘤患者的原发肿瘤均显示(18)F-FAZA摄取非常高。9例HNSCC患者中有6例，在原发肿瘤和/或颈部淋巴结中观察到(18)F-FAZA的明显摄取。21例淋巴瘤患者（15例非霍奇金淋巴瘤和6例霍奇金病）中，3例显示与淋巴瘤相关的中度摄取。13例肺癌患者（12例NSCLC，1例SCLC）中，7例原发肺肿瘤的(18)F-FAZA摄取增加。未观察到(18)F-FAZA给药的副作用。
本研究表明，(18)F-FAZA可能是一种非常有用的放射性药物，可对所选肿瘤类型中的缺氧情况进行成像。特别是胶质瘤的高摄取令人鼓舞。鉴于其良好的成像特性，包括在所研究肿瘤类别中可接受的T/B比值，(18)F-FAZA可被视为评估这些肿瘤类型缺氧分数的非常有前景的药物。
