Background

Microdialysis is a well validated sampling technique that can be used for pharmacokinetic studies of oncological drugs targeting the central nervous system. This technique has also been applied to evaluate tumor metabolism and identify pharmacodynamic biomarkers of drug activity. Despite the potential utility of microdialysis for therapeutic discovery, variability in tumor size and location hamper routine use of microdialysis as a preclinical tool. Quantitative validation of microdialysis membrane location relative to radiographically evident tumor regions could facilitate rigorous preclinical studies. However, a widely accessible standardized workflow for preclinical catheter placement and validation is needed.

New method

We provide methods for a workflow to yield tailored placement of microdialysis probes within a murine intracranial tumor and illustrate in an IDH1-mutant patient-derived xenograft (PDX) model. This detailed workflow uses a freely available on-line tool built within 3D-slicer freeware to target microdialysis probe placement within the tumor core and validate probe placement fully within the tumor.

Results

We illustrate use of this workflow to validate microdialysis probe location relative to implanted IDH1-mutant PDXs, using the microdialysis probes to quantify levels of extracellular onco-metabolite D-2 hydroxyglutarate.

Comparison with existing methods

Previous methods have used 3D slicer to reliably measure tumor volumes. Prior microdialysis studies have targeted expected tumor locations without validation.

Conclusions

The new method offers a streamlined and freely available workflow in 3D slicer to optimize and validate microdialysis probe placement within a murine brain tumor.

中文翻译：

---

小鼠脑肿瘤模型中肿瘤内微透析探针靶向和验证的方法

背景

微透析是一种经过充分验证的采样技术，可用于针对中枢神经系统的肿瘤药物的药代动力学研究。该技术还被应用于评估肿瘤代谢和鉴定药物活性的药效学生物标志物。尽管微透析在治疗发现中具有潜在效用，但肿瘤大小和位置的可变性阻碍了微透析作为临床前工具的常规使用。相对于放射学明显肿瘤区域的微透析膜位置的定量验证可以促进严格的临床前研究。然而，需要广泛使用的用于临床前导管放置和验证的标准化工作流程。

新方法

我们提供了一种工作流程方法，可在小鼠颅内肿瘤内定制微透析探针的放置，并在 IDH1 突变的患者来源异种移植 (PDX) 模型中进行说明。这个详细的工作流程使用内置于 3D 切片器免费软件中的免费在线工具，将微透析探针定位在肿瘤核心内，并完全验证探针在肿瘤内的定位。

结果

我们说明了使用此工作流程来验证相对于植入的 IDH1 突变 PDX 的微透析探针位置，使用微透析探针来量化细胞外肿瘤代谢物 D-2 羟基戊二酸的水平。

与现有方法的比较

以前的方法使用 3D 切片器来可靠地测量肿瘤体积。先前的微透析研究针对预期的肿瘤位置而未经验证。

结论

新方法在 3D 切片机中提供了一个简化且免费可用的工作流程，以优化和验证小鼠脑肿瘤内的微透析探针放置。