使用18F-氟米索硝唑和64Cu（II）-二乙酰基双（N4-甲基硫代半卡巴腙）正电子发射断层扫描评估局部肿瘤缺氧：在R3327-AT和FaDu大鼠肿瘤模型中进行的包括微型PET成像、氧分压探针测量、放射自显影和荧光显微镜检查的比较研究。

Assessment of regional tumor hypoxia using 18F-fluoromisonidazole and 64Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) positron emission tomography: Comparative study featuring microPET imaging, Po2 probe measurement, autoradiography, and fluorescent microscopy in the R3327-AT and FaDu rat tumor models.

作者信息

O'Donoghue Joseph A, Zanzonico Pat, Pugachev Andrei, Wen Bixiu, Smith-Jones Peter, Cai Shangde, Burnazi Eva, Finn Ronald D, Burgman Paul, Ruan Shutian, Lewis Jason S, Welch Michael J, Ling C Clifton, Humm John L

机构信息

Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

出版信息

Int J Radiat Oncol Biol Phys. 2005 Apr 1;61(5):1493-502. doi: 10.1016/j.ijrobp.2004.12.057.

DOI:10.1016/j.ijrobp.2004.12.057

PMID:15817355

Abstract

PURPOSE

To compare two potential positron emission tomography (PET) tracers of tumor hypoxia in an animal model.

METHODS AND MATERIALS

The purported hypoxia imaging agents (18)F-fluoromisonidazole (FMISO) and (64)Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) were compared by serial microPET imaging of Fisher-Copenhagen rats bearing the R3327-AT anaplastic rat prostate tumor. Probe measurements of intratumoral Po(2) were compared with the image data. At the microscopic level, the relationship between the spatial distributions of (64)Cu (assessed by digital autoradiography) and tumor hypoxia (assessed by immunofluorescent detection of pimonidazole) was examined. (18)F-FMISO and (64)Cu-ATSM microPET images were also acquired in nude rats bearing xenografts derived from the human squamous cell carcinoma cell line, FaDu.

RESULTS

In R3327-AT tumors, the intratumoral distribution of (18)F-FMISO remained relatively constant 1-4 h after injection. However, that of (64)Cu-ATSM displayed a significant temporal evolution for 0.5-20 h after injection in most tumors. In general, only when (64)Cu-ATSM was imaged at later times (16-20 h after injection) did it correspond to the distribution of (18)F-FMISO. Oxygen probe measurements were broadly consistent with (18)F-FMISO and late (64)Cu-ATSM images but not with early (64)Cu-ATSM images. At the microscopic level, a negative correlation was found between tumor hypoxia and (64)Cu distribution when assessed at early times and a positive correlation when assessed at later times. For the FaDu tumor model, the early and late (64)Cu-ATSM microPET images were similar and were in general concordance with the (18)F-FMISO scans.

CONCLUSION

The difference in behavior between the R3327-AT and FaDu tumor models suggests a tumor-specific dependence of Cu-ATSM uptake and retention under hypoxic conditions.

摘要

目的

在动物模型中比较两种潜在的肿瘤缺氧正电子发射断层扫描（PET）示踪剂。

方法与材料

通过对携带R3327-AT间变性大鼠前列腺肿瘤的Fisher-哥本哈根大鼠进行连续微PET成像，比较了所谓的缺氧显像剂（18）F-氟米索硝唑（FMISO）和（64）Cu（II）-二乙酰双（N4-甲基硫代半卡巴腙）（Cu-ATSM）。将瘤内Po(2)的探针测量结果与图像数据进行比较。在微观层面，研究了（64）Cu的空间分布（通过数字放射自显影评估）与肿瘤缺氧（通过匹莫硝唑的免疫荧光检测评估）之间的关系。还在携带源自人鳞状细胞癌细胞系FaDu的异种移植物的裸鼠中获取了（18）F-FMISO和（64）Cu-ATSM微PET图像。

结果

在R3327-AT肿瘤中，注射后1-4小时内，（18）F-FMISO在瘤内的分布保持相对恒定。然而，在大多数肿瘤中，（64）Cu-ATSM的分布在注射后0.5-20小时内呈现出显著的时间演变。一般来说，只有当（64）Cu-ATSM在较晚时间（注射后16-20小时）成像时，它才与（18）F-FMISO的分布相对应。氧探针测量结果与（18）F-FMISO和晚期（64）Cu-ATSM图像大致一致，但与早期（64）Cu-ATSM图像不一致。在微观层面，早期评估时发现肿瘤缺氧与（64）Cu分布呈负相关，晚期评估时呈正相关。对于FaDu肿瘤模型，早期和晚期（64）Cu-ATSM微PET图像相似，总体上与（18）F-FMISO扫描结果一致。