用于通过19F磁共振波谱（19F-MRS）测量肿瘤缺氧的新型非侵入性探针。在SCCVII/C3H小鼠模型中的研究。

Novel non-invasive probes for measuring tumor-hypoxia by 19F-magnetic resonance spectroscopy (19F-MRS). Studies in the SCCVII/C3H murine model.

作者信息

Papadopoulou Maria V, Pouremad Reza, Bloomer William D, Wyrwicz Alice

机构信息

Evanston Northwestern Healthcare, Department of Radiation Medicine, 2650 Ridge Avenue, Evanston, IL 60201, USA.

出版信息

Anticancer Res. 2006 Sep-Oct;26(5A):3259-63.

PMID:17094438

Abstract

BACKGROUND

19F-labeled 2-nitroimidazoles bound to hypoxic cells in tumors are known to be useful probes for measuring hypoxia since they can allow for their non-invasive detection by 19F nuclear magnetic resonance, provided that they do not lose 19F during their hypoxia-mediated metabolism. Two such compounds, N-(m-trifluoromethylbenzyl)-3-(2-nitro-1-imidazolyl)-propylamine hydrochloride (mTFN-1) and 5,6-dimethyl-4-[3-(2-nitro-1-imidazolyl)-propylamino]-2-trifluoromethylpyrimidine hydrochloride (CF3PM) were selected from a series of analogs, for their in vivo evaluation, based on their high solubility in saline and low toxicity in mice.

MATERIALS AND METHODS

MRS experiments were performed in anesthetized C3H mice bearing SCCVII tumors in their flanks. Fluorinated compounds, mTFN-1 or CF3PM, were injected intraperitoneally (i.p.) at a dose of 110 or 150 mg/kg, respectively, in 0.75 mL saline. A 0.9 cm surface coil tuned to fluorine frequency was positioned directly over the tumor, the head, or the liver and 1800 transients were collected over 20 min in a Bruker Omega 4.7 T instrument. Spectroscopic measurements were taken at 2, 7 and 19 h post injection of the fluorinated drug.

RESULTS

CF3PM was detected in the plasma up to 2 h post injection with maximum concentration observed 30 min post administration. In the MRS studies, mTFN-1 signal in the tumor was 68.8, 86.8 and 27.2% of the reference at 1-2, 6-7 and 18-19 h post injection, respectively. The corresponding values in the brain were 0, 125.7 and 26.6%, respectively, whereas the corresponding values in the liver were 359.3, 307.7 and 0%, respectively. CF3PM signal in the tumor was 3.3, 57.7 and 7.1% of the reference at 1-2, 6-7 and 18-19 h post injection, respectively. The corresponding values in the liver were 267.6, 60.5 and 0%, respectively. No CF3PM signal was detected in the brain at any time interval.

CONCLUSION

These results suggest that CF3PM could be used as a potential probe for measuring hypoxia in tumors by 19F-MRS.

摘要

背景

已知与肿瘤中的缺氧细胞结合的19F标记的2-硝基咪唑是用于测量缺氧的有用探针，因为只要它们在缺氧介导的代谢过程中不损失19F，就可以通过19F核磁共振对其进行非侵入性检测。从一系列类似物中选择了两种这样的化合物，即N-（间三氟甲基苄基）-3-（2-硝基-1-咪唑基）-丙胺盐酸盐（mTFN-1）和5,6-二甲基-4-[3-（2-硝基-1-咪唑基）-丙氨基]-2-三氟甲基嘧啶盐酸盐（CF3PM），基于它们在盐水中的高溶解度和对小鼠的低毒性进行体内评估。

材料与方法

在麻醉的C3H小鼠侧腹接种SCCVII肿瘤后进行磁共振波谱（MRS）实验。将氟化化合物mTFN-1或CF3PM分别以110或150mg/kg的剂量腹腔注射到0.75mL盐水中。将一个调谐到氟频率的0.9cm表面线圈直接放置在肿瘤、头部或肝脏上方，并在Bruker Omega 4.7T仪器中20分钟内采集1800个瞬态信号。在注射氟化药物后2、7和19小时进行光谱测量。

结果

注射后2小时内血浆中可检测到CF3PM，给药后30分钟观察到最大浓度。在MRS研究中，注射后1-2、6-7和18-19小时，肿瘤中mTFN-1信号分别为参比信号的68.8%、86.8%和27.2%。大脑中的相应值分别为0%、125.7%和26.6%，而肝脏中的相应值分别为359.3%、307.7%和0%。注射后1-2、6-7和18-个月19小时，肿瘤中CF3PM信号分别为参比信号的3.3%、57.7%和7.1%。肝脏中的相应值分别为267.6%、60.5%和0%。在任何时间间隔内大脑中均未检测到CF3PM信号。