使用18F-氟阿糖胞苷进行缺氧特异性肿瘤成像。

Hypoxia-specific tumor imaging with 18F-fluoroazomycin arabinoside.

作者信息

Piert Morand, Machulla Hans-Jürgen, Picchio Maria, Reischl Gerald, Ziegler Sybille, Kumar Piyush, Wester Hans-Jürgen, Beck Roswitha, McEwan Alexander J B, Wiebe Leonard I, Schwaiger Markus

机构信息

Nuclear Medicine Clinic, Technical University of Munich, Munich, Germany.

出版信息

J Nucl Med. 2005 Jan;46(1):106-13.

PMID:15632040

Abstract

UNLABELLED

The study was performed to compare the (18)F-labeled nitroimidazole compound fluoroazomycin arabinoside ((18)F-FAZA) with the standard hypoxia tracer fluoromisonidazole ((18)F-FMISO) in detection of tumor tissue hypoxia and to verify the oxygenation dependency of (18)F-FAZA uptake.

METHODS

Biodistribution of (18)F-FAZA was studied at various time points in EMT6 tumor-bearing BALB/c mice and in AR42J and A431 tumor-bearing nude mice and compared with that of (18)F-FMISO. The presence of tumor tissue hypoxia was verified in 5 EMT6 and 5 AR42J tumors using an oxygen-sensing needle electrode system. To evaluate the oxygenation dependency of (18)F-FAZA uptake, using the Munich prototype animal PET scanner, 2 serial PET scans were performed in 13 A431 tumor-bearing nude mice breathing pure oxygen or room air on 1 d and then selecting the other oxygen breathing condition on the following day. In addition, digital autoradiography was performed with EMT6 tumor-bearing (18)F-FAZA-dosed, nude mice breathing either room air (n = 8) or carbogen (n = 9).

RESULTS

Tissue partial pressure of oxygen (Po(2)) electrode measurements revealed that tumor hypoxia was present under room air breathing in EMT6 (tissue Po(2) = 2.9 +/- 2.6) and AR42J tumors (tissue Po(2) = 0.4 +/- 0.2), which was significantly lower compared with that of reference tissue (tissue Po(2) = 25.8 +/- 6.7 and tissue Po(2) = 29.0 +/- 3.0 [mean +/- SD], respectively; P < 0.01). In all tumor models, (18)F-FAZA displayed significantly higher tumor-to-muscle and tumor-to-blood ratios compared with (18)F-FMISO, indicating a faster clearance of (18)F-FAZA from normal tissues. In AR42J tumors, (18)F-FAZA tumor-to-normal ratios were found to increase over time. Serial animal (18)F-FAZA PET studies showed that the tumor-to-background ratio was significantly higher in animals breathing room air compared with that of animals breathing pure oxygen (7.3 +/- 2.3 vs. 4.2 +/- 1.2, respectively; P < 0.001). Similarly, autoradiography showed significantly higher tumor-to-muscle ratios in mice breathing room air compared with those of animals breathing carbogen (5.3 +/- 0.8 vs. 2.2 +/- 0.8; respectively; P < 0.02).

CONCLUSION

(18)F-FAZA shows superior biokinetics and is, thus, a promising PET tracer for the visualization of tumor hypoxia. This study also verified a hypoxia-specific uptake mechanism for (18)F-FAZA in murine tumor models.

摘要

未标记

本研究旨在比较（18）F标记的硝基咪唑化合物氟阿糖胞苷（（18）F-FAZA）与标准缺氧示踪剂氟米索硝唑（（18）F-FMISO）在检测肿瘤组织缺氧方面的效果，并验证（18）F-FAZA摄取的氧合依赖性。

方法

在荷EMT6肿瘤的BALB/c小鼠、荷AR42J肿瘤的裸鼠和荷A431肿瘤的裸鼠的不同时间点研究（18）F-FAZA的生物分布，并与（18）F-FMISO的生物分布进行比较。使用氧传感针电极系统在5个EMT6肿瘤和5个AR42J肿瘤中验证肿瘤组织缺氧的存在。为了评估（18）F-FAZA摄取的氧合依赖性，使用慕尼黑原型动物PET扫描仪，对13只荷A431肿瘤的裸鼠进行连续2次PET扫描，这些裸鼠在第1天呼吸纯氧或室内空气，然后在第二天选择另一种吸氧条件。此外，对呼吸室内空气（n = 8）或卡波金（n = 9）的荷EMT6肿瘤且注射了（18）F-FAZA的裸鼠进行数字放射自显影。

结果

组织氧分压（Po₂）电极测量显示，在呼吸室内空气的情况下，EMT6肿瘤（组织Po₂ = 2.9 ± 2.6）和AR42J肿瘤（组织Po₂ = 0.4 ± 0.2）中存在肿瘤缺氧，与参考组织相比显著更低（参考组织的组织Po₂分别为25.8 ± 6.7和29.0 ± 3.0[平均值±标准差]；P < 0.01）。在所有肿瘤模型中，与（18）F-FMISO相比，（18）F-FAZA显示出显著更高的肿瘤与肌肉以及肿瘤与血液的比值，表明（18）F-FAZA从正常组织中的清除更快。在AR42J肿瘤中，发现（18）F-FAZA的肿瘤与正常组织比值随时间增加。连续的动物（18）F-FAZA PET研究表明，呼吸室内空气的动物的肿瘤与背景比值显著高于呼吸纯氧的动物（分别为7.3 ± 2.3和4.2 ± 1.2；P < 0.001）。同样，放射自显影显示，呼吸室内空气的小鼠的肿瘤与肌肉比值显著高于呼吸卡波金的动物（分别为5.3 ± 0.8和2.2 ± 0.8；P < 0.02）。