IMAGING OF HYPOXIA IN HUMAN TUMORS WITH [F-18] FLUOROMISONIDAZOLE
IMAGING OF HYPOXIA IN HUMAN TUMORS WITH [F-18] FLUOROMISONIDAZOLE
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DOI：
10.1016/0360-3016(92)91001-4
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发表时间：
1992-01-01
影响因子：
7
通讯作者：
GRIFFIN, TW
中科院分区：
文献类型：
--
作者：
KOH, WJ;RASEY, JS;GRIFFIN, TW
氟异硝唑(FMISO)已被证明在体外和体内具有放射生物学意义的氧气水平下选择性地与低氧细胞结合。当用正电子发射体氟-18(F-18)标记后，正电子发射断层扫描(PETT)可以高精度地定量检测其在组织中的摄取。本文介绍了人类恶性肿瘤摄取[F-18]FMISO的PETT成像的第一次经验，并描述了该技术作为一种非侵入性评估肿瘤缺氧的工具的发展。8名癌症患者在初次放射治疗前接受了成像，3名患者返回进行后续扫描，总共进行了11次成像研究。放射治疗前的8项研究中有6项显示，在注射药物后2小时，肿瘤中[F-18]FMISO的滞留率显著超过血浆浓度；所有5名头颈部原发肿瘤患者的扫描结果都是“阳性”的。提出了一种解释[F-18]FMISO PETT图像的分析方法，将肿瘤体积内的缺氧元素定义为具有阈值区域肿瘤的区域：注射后2小时或更长时间的血浆[F-18]FMISO比率大于或等于1.4。在一个分割放射治疗疗程接近尾声时，对扫描结果最初呈阳性的患者进行的三项重复研究显示，肿瘤内药物的积聚没有超过1.4的阈值比率，这表明已经发生了复氧。药代动力学和剂量学数据支持继续使用[F-18]FMISO作为安全的低氧探测器。已经开发了两种用于人体研究的成像方案；长方案允许更完整的生物分布和剂量信息，而较短的方案通过应用简单的、临床上方便的成像程序来促进增加患者的收益。当与肿瘤预后相关时，[F-18]FMISO PETT成像可作为肿瘤对常规放射治疗反应的预测指标。讨论了这项技术在解决人类肿瘤学中肿瘤缺氧的长期问题上的意义。
Fluoromisonidazole (FMISO) has been shown to bind selectively to hypoxic cells in vitro and in vivo at radiobiologically significant oxygen levels. When labeled with the positron emitter fluorine-18 (F-18), its uptake in tissue can be detected quantitatively with high precision by positron emission transaxial tomography (PETT). This paper presents the first experiences with PETT imaging of [F-18]FMISO uptake in human malignancies, and describes the development of this technique as a tool for the non-invasive assessment of tumor hypoxia. Eight patients with selected cancers were imaged prior to primary radiotherapy, and 3 returned for follow-up scans, for a total of 11 imaging studies. Six of eight pre-radiotherapy studies revealed retention of [F-18]FMISO in tumors that significantly exceeded plasma concentrations by 2 hr after drug injection; all five patients with head and neck primaries had such "positive" scans. An analytic method for the interpretation of [F-18] FMISO PETT images is presented, defining hypoxic elements within a tumor volume as regions with a threshold regional tumor:plasma [F-18]FMISO ratio of greater-than-or-equal to 1.4 by 2 or more hours after injection. Toward the end of a course of fractionated radiotherapy, three repeat studies in patients with initially positive scans showed no tumor accumulation of drug above the threshold ratio of 1.4, suggesting reoxygenation had occurred. Pharmacokinetic and dosimetry data support continued use of [F-18]FMISO as a safe hypoxia probe. Two imaging protocols have been developed for human studies; a long protocol allows for more complete biodistribution and dosimetry information, and a shorter protocol facilitates increased patient accrual by applying a simple, clinically expedient imaging procedure. When correlated with tumor outcome, [F-18]FMISO PETT imaging may be developed as a predictor of tumor response to conventional radiotherapy. The implications of this technique in addressing persistent questions of tumor hypoxia in human oncology is discussed.