Therapeutic efficacy of DTI-015 using diffusion magnetic resonance imaging as an early surrogate marker
Therapeutic efficacy of DTI-015 using diffusion magnetic resonance imaging as an early surrogate marker
复制标题
DOI：
10.1158/1078-0432.ccr-04-1218
复制
发表时间：
2004-12-01
影响因子：
11.5
通讯作者：
Ross, BD
中科院分区：
文献类型：
--
作者：
Hall, DE;Moffat, BA;Ross, BD
为了研究扩散加权磁共振成像作为定量替代标记物，用于评估原位实验性神经胶质瘤模型中治疗诱导的细胞变化，用直接肿瘤内DTI-015治疗肿瘤，该肿瘤是1,3-BIS的溶液（2--三） 100％EtOH中的氯乙基）-1-硝基库（BCNU）。在Fischer 344大鼠中诱导了脑内9L肿瘤，并建立了三个治疗组：DTI-015，ETOH和假。在立体定向指导下，两组大鼠在ETOH中接受了肿瘤内注射67 mg/mL BCNU或单独的ETOH的肿瘤体积的50％，最多为30 mUl。在治疗前和在1、24、48和72小时的处理之前，在处理之前获取扩散磁共振图像，然后每周3次。使用扩散加权的横向磁共振图像和每个肿瘤的直方图图像，使用多切片扩散加权磁共振成像检查肿瘤细胞活力。对照动物（经eTOH或假处理的动物）显示出平均表观扩散系数（ADC），在实验时间过程中基本上保持不变。相比之下，用DTI-015处理的大鼠在24小时内与预处理相对于预处理显示出显着增加，随后肿瘤量收缩，囊性区域的发展以及随后的治疗反应进一步增加，随后有明显的治疗反应，并且证明了这一点。增强的动物生存。最后，不仅ADC测量值可以预测治疗组之间的差异，而且还产生了有关在个别治疗的动物中治疗功效的空间和时间数据，这些数据可用于指导后续治疗。
To investigate diffusion weighted magnetic resonance imaging as a quantitative surrogate marker for evaluating the therapy-induced cellular changes in an orthotopic experimental glioma model, tumors were treated with direct intratumoral administration of DTI-015, a solution of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in 100% EtOH. Intracerebral 9L tumors were induced in Fischer 344 rats, and three treatment groups were established: DTI-015, EtOH, and sham. Two groups of rats received intratumoral injection of either 67 mg/mL BCNU in EtOH or EtOH alone at 50% of the tumor volume up to a maximum of 30 mul under stereotactic guidance. Diffusion magnetic resonance images were acquired before treatment and after treatment at 1, 24, 48, and 72 hours and then 3 times per week thereafter. Tumor cell viability was examined using multi-slice diffusion weighted magnetic resonance imaging with diffusion weighted transverse magnetic resonance images and histogram plots of each tumor quantified over time. Control animals (EtOH- or sham-treated animals) showed mean apparent diffusion coefficients (ADCs) that remained essentially unchanged over the experimental time course. In contrast, rats treated with DTI-015 showed a significant increase in ADC relative to the pretreatment within 24 hours, which further increased over time, followed by a significant therapeutic response as evidenced by subsequent tumor volume shrinkage, development of a cystic region, and enhanced animal survival. Finally, not only were ADC measurements predictive of differences between treatment groups, but they also yielded spatial and temporal data regarding the efficacy of treatment within individual treated animals that could be used to guide subsequent therapy.