Department of Surgical and Radiological of Sciences, School of Veterinary Medicine, University of California-Davis, Davis, California 95616-8745, USA.
Neuro Oncol. 2010 Sep;12(9):928-40. doi: 10.1093/neuonc/noq046. Epub 2010 May 20.
Canine spontaneous intracranial tumors bear striking similarities to their human tumor counterparts and have the potential to provide a large animal model system for more realistic validation of novel therapies typically developed in small rodent models. We used spontaneously occurring canine gliomas to investigate the use of convection-enhanced delivery (CED) of liposomal nanoparticles, containing topoisomerase inhibitor CPT-11. To facilitate visualization of intratumoral infusions by real-time magnetic resonance imaging (MRI), we included identically formulated liposomes loaded with Gadoteridol. Real-time MRI defined distribution of infusate within both tumor and normal brain tissues. The most important limiting factor for volume of distribution within tumor tissue was the leakage of infusate into ventricular or subarachnoid spaces. Decreased tumor volume, tumor necrosis, and modulation of tumor phenotype correlated with volume of distribution of infusate (Vd), infusion location, and leakage as determined by real-time MRI and histopathology. This study demonstrates the potential for canine spontaneous gliomas as a model system for the validation and development of novel therapeutic strategies for human brain tumors. Data obtained from infusions monitored in real time in a large, spontaneous tumor may provide information, allowing more accurate prediction and optimization of infusion parameters. Variability in Vd between tumors strongly suggests that real-time imaging should be an essential component of CED therapeutic trials to allow minimization of inappropriate infusions and accurate assessment of clinical outcomes.
犬自发性颅内肿瘤与人类肿瘤具有惊人的相似之处，并且有可能为新型治疗方法的更现实验证提供大型动物模型系统，这些方法通常是在小型啮齿动物模型中开发的。我们使用自发性发生的犬神经胶质瘤来研究脂质体纳米颗粒（包含拓扑异构酶抑制剂 CPT-11）的对流增强输送（CED）的应用。为了通过实时磁共振成像（MRI）促进对肿瘤内输注的可视化，我们包含了相同配方的载有 Gadoteridol 的脂质体。实时 MRI 定义了输注物在肿瘤和正常脑组织内的分布。在肿瘤组织内分布体积的最重要限制因素是输注物漏入脑室或蛛网膜下腔。肿瘤体积减小、肿瘤坏死以及肿瘤表型的调节与输注物的分布体积（Vd）、输注位置和实时 MRI 和组织病理学确定的渗漏相关。这项研究表明，犬自发性神经胶质瘤具有作为人类脑肿瘤新型治疗策略验证和开发的模型系统的潜力。通过在大型自发性肿瘤中实时监测输注获得的数据可能提供信息，从而更准确地预测和优化输注参数。肿瘤之间 Vd 的可变性强烈表明，实时成像应该是 CED 治疗试验的一个重要组成部分，以允许最小化不适当的输注并准确评估临床结果。
