Chen Limin, Zhang Zhengwei, Kolb Hartmuth C, Walsh Joseph C, Zhang James, Guan Yihui
PET Center, Huashan Hospital, Fudan University, Shanghai, China.
Nucl Med Commun. 2012 Oct;33(10):1096-102. doi: 10.1097/MNM.0b013e3283571016.
Hypoxia is an important negative prognostic factor for radiation treatment of head and neck (H&N) cancer. The focus of this study was to evaluate the feasibility of 18F-HX4 (3-[18F]fluoro-2-(4-((2-nitro-1Himidazol- 1-yl)methyl)-1H-1,2,3,-triazol-1-yl)-propan-1-ol) on hypoxia imaging compared with 18F-fluoromisonidazole (18F-FMISO) mainly in human H&N cancer.
18F-HX4 precursor, standards, and methods were provided by Siemens Molecular Imaging Inc. 18F-HX4 was prepared in an automated module. Twelve patients with H&N cancer were recruited into this study. Each patient underwent 18F-HX4 PET/CT imaging, followed by 18F-FMISO and 18F-fluorodeoxyglucose (18F-FDG) PET/CT on separate days. 18F-HX4 and 18F-FMISO images of the H&N areas were acquired 1.5 and 2 h after injection, respectively. Standard uptake values and tumor-to-muscle (T/M) ratios were calculated. Immunohistochemical analysis of the hypoxia-associated marker CA-IX was carried out to investigate the relationship with PET uptake.
18F-HX4 and 18F-FMISO in the patients gave similar hot spots well within the 18F-FDG uptake region. At 1.5 h postinjection 18F-HX4 yielded a T/M similar to that of 18F-FMISO at 2 h postinjection (1.94±1.03 vs. 1.85±1.01; P> 0.05). A total of 12 lesions were identified. Among them, eight lesions were positive and two lesions were negative on both 18F-HX4 and 18F-FMISO images; one of the other two lesions was positive only on 18F-HX4, whereas the other one was positive only on 18F-FMISO. The CA-IX expression result correlated with the hypoxia imaging but not with 18F-FDG imaging.
18F-HX4 is a safe and feasible agent in hypoxia imaging of H&N cancer patients. We could assume that 18F-HX4 may have higher sensitivity and specificity, faster clearance, and shorter injection–acquisition time compared with traditional 18F-FMISO. Additional evaluations need to be carried out to validate the assumption. Further development of 18F-HX4 for eventual targeting of antihypoxia therapies is warranted.
缺氧是头颈部（H&N）癌放射治疗的一个重要不良预后因素。本研究的重点是评估18F-HX4（3-[18F]氟-2-(4-((2-硝基-1H-咪唑-1-基)甲基)-1H-1,2,3,-三唑-1-基)-丙-1-醇）在缺氧成像方面的可行性，并与主要用于人类H&N癌的18F-氟米索硝唑（18F-FMISO）进行比较。
18F-HX4前体、标准品和方法由西门子分子影像公司提供。18F-HX4在一个自动化模块中制备。12例H&N癌患者被纳入本研究。每位患者先进行18F-HX4 PET/CT成像，随后在不同日期分别进行18F-FMISO和18F-氟脱氧葡萄糖（18F-FDG）PET/CT成像。分别在注射后1.5小时和2小时采集H&N区域的18F-HX4和18F-FMISO图像。计算标准摄取值和肿瘤与肌肉（T/M）比值。对缺氧相关标志物CA-IX进行免疫组化分析，以研究其与PET摄取的关系。
患者体内的18F-HX4和18F-FMISO在18F-FDG摄取区域内产生了相似的热点。注射后1.5小时，18F-HX4产生的T/M与注射后2小时的18F-FMISO相似（1.94±1.03对1.85±1.01；P>0.05）。共识别出12个病灶。其中，8个病灶在18F-HX4和18F-FMISO图像上均为阳性，2个病灶均为阴性；另外2个病灶中的一个仅在18F-HX4上为阳性，而另一个仅在18F-FMISO上为阳性。CA-IX表达结果与缺氧成像相关，但与18F-FDG成像无关。
18F-HX4在H&N癌患者的缺氧成像中是一种安全可行的药物。我们可以假设，与传统的18F-FMISO相比，18F-HX4可能具有更高的敏感性和特异性、更快的清除率以及更短的注射-采集时间。需要进行额外的评估来验证这一假设。18F-HX4用于最终靶向抗缺氧治疗的进一步开发是有必要的。
