In vivo 19F magnetic resonance spectroscopy and chemical shift imaging of tri-fluoro-nitroimidazole as a potential hypoxia reporter in solid tumors.
In vivo 19F magnetic resonance spectroscopy and chemical shift imaging of tri-fluoro-nitroimidazole as a potential hypoxia reporter in solid tumors.
复制标题
三氟硝基咪唑作为实体瘤潜在缺氧报告基因的体内 19F 磁共振波谱和化学位移成像。
DOI：
10.1158/1078-0432.ccr-06-1563
复制
发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Koutcher,JasonA
中科院分区：
文献类型：
--
作者：
Procissi,Daniel;Claus,Filip;Burgman,Paul;Koziorowski,Jacek;Chapman,JDonald;Thakur,SunithaB;Matei,Cornelia;Ling,CClifton;Koutcher,JasonA
目的：利用19 F磁共振波谱（MRS）和19 F化学位移成像研究2-硝基-α-[（2，2，2-三氟乙氧基）甲基]-咪唑-1-乙醇（TF-MISO）作为肿瘤组织氧水平的潜在非侵入性标记物。实验设计：在不同氧条件下孵育的肿瘤细胞上使用高效液相色谱法获得体外数据以确定氧结合特征。除了在裸鼠移植的大鼠前列腺肿瘤模型（R3327-AT）上的研究之外，还使用充分表征的缺氧小鼠乳腺肿瘤（MCa）获得体内数据。在75 mg/kg静脉注射后，使用MRS检测TF-MISO的肿瘤内19 F信号长达10 h。局部分布的化合物在植入的MCa肿瘤已被成像使用切片选择性二维化学位移imaging 6 h后injecting.Results：Thein vitroresults表明，TF-MISO优先积累在缺氧条件下培养的细胞。体内19 F MR光谱特征（线宽和化学位移）被记录为注射后时间的函数，结果表明氟原子确实对局部环境的变化敏感，同时仍然提供可检测的MR信号。从19 F MRS获得的晚期时间点（>6小时）肿瘤组织浓度表明，TF-MISO减少并保留在缺氧肿瘤中。获得TF-MISO肿瘤分布图在一个合理的时间框架的可行性established.Conclusions：基于本文提出的结果，它表明，TF-MISO有可能成为一个有效的磁共振缺氧成像报告临床前缺氧研究和缺氧导向的临床治疗。
Purpose:2-Nitro-α-[(2,2,2-trifluoroethoxy)methyl]-imidazole-1-ethanol (TF-MISO) was investigated as a potential noninvasive marker of tissue oxygen levels in tumors using19F magnetic resonance spectroscopy (MRS) and19F chemical shift imaging.Experimental Designs:In vitrodata were obtained using high-performance liquid chromatography on tumor cells incubated under varying oxygen conditions to determine the oxygen-binding characteristics.In vivodata were obtained using a well-characterized hypoxic murine breast tumor (MCa), in addition to studies on a rat prostate tumor model (R3327-AT) implanted in nude mice. Detection of intratumor19F signal from TF-MISO was done using MRS for up to 10 h following a 75 mg/kg i.v. injection. Localized distribution of the compound in the implanted MCa tumor has been imaged using slice-selective two-dimensional chemical shift imaging 6 h after injection.Results:Thein vitroresults showed that TF-MISO preferentially accumulates in cells incubated under anoxic conditions. Thein vivo19F MR spectral features (line width and chemical shift) were recorded as a function of time after injection, and the results indicate that the fluorine atoms are indeed sensitive to changes in the local environment while still providing a detectable MR signal.Ex vivospectra were collected and established the visibility of the19F signal under conditions of maximum hypoxia. Late time point (>6 h) tumor tissue concentrations, as obtained from19F MRS, suggest that TF-MISO is reduced and retained in hypoxic tumor. The feasibility of obtaining TF-MISO tumor distribution maps in a reasonable time frame was established.Conclusions:Based on the results presented herein, it is suggested that TF-MISO has the potential to be a valid magnetic resonance hypoxia imaging reporter for both preclinical hypoxia studies and hypoxia-directed clinical therapy.