文章：

乳腺癌脑膜转移模型：体内分子成像表征

A model of breast cancer meningeal metastases: characterization with in vivo molecular imaging

原文发布日期：2018-11-13

英文摘要：

Meningeal metastasis is a fatal complication of breast cancer which affects 8–15% of patients who experience severe neurological complications of cranial nerves, cerebrum, and spinal cord. Survival once diagnosed is less than 4 months. Currently there is no cure. Aggressive multimodal radiation, intra-CSF, or systemic chemotherapy is palliative. Investigation of urgently needed new treatment modalities is hindered by the lack of suitable animal models to effectively study tumor growth kinetics. We present a model of meningeal metastases where tumor growth and associated neurological symptoms have been characterized over 3 weeks by sequential molecular imaging, tumor growth kinetics, and histopathology. Meningeal metastases were induced by stereotaxic injection of human breast cancer cells (MDA-MB-231-Rluc) into the lateral ventricle. Tumor identified by Gd-MRI and Rluc-bioluminescence depict growth in 3 phases, namely lag, exponential, and plateau phase. Invasive tumor growth was highlighted by changes in contrast distribution in the meninges, ventricle and brain compartments over time where moderate contrast uptake in the early growth phase gave rise to a heavy tumor burden in the base of the brain in the latter phases. Tumor growth was accompanied with debilitating neurological symptoms and change in body mass. Tumor was confirmed by ex vivo histology. The reliability of the model to study novel therapeutics was confirmed by oncolytic virus delivered into the lateral ventricle showed potential for treatment. This effective and reliable model resembles human disease progression and is ideally suited to investigate novel treatments. 

摘要翻译：

脑膜转移是乳腺癌的一种致命并发症，约8-15%的患者会因颅神经、大脑及脊髓受累出现严重神经系统症状。一经确诊，患者生存期通常不足4个月，且目前尚无治愈手段。激进的多模式放疗、脑脊液内化疗或全身性化疗仅能缓解症状。由于缺乏能有效模拟肿瘤生长动力学的合适动物模型，亟需的新治疗方案研究受阻。本研究通过连续分子影像、肿瘤生长动力学和组织病理学分析，构建了可在三周内呈现肿瘤生长轨迹及相关神经系统症状的脑膜转移模型。通过立体定向注射人乳腺癌细胞（MDA-MB-231-Rluc）至侧脑室成功诱导脑膜转移，钆增强MRI和荧光素酶生物发光成像显示肿瘤生长经历三个典型阶段：停滞期、指数生长期和平稳期。随病程进展，脑膜、脑室及脑实质内对比剂分布的变化揭示了侵袭性肿瘤生长模式——早期轻度对比剂摄取逐渐发展为后期脑底部大量肿瘤负荷。肿瘤生长伴随进行性神经系统症状恶化及体重变化，并经离体组织学证实。通过侧脑室注射溶瘤病毒验证该模型用于新疗法研究的可靠性，结果显示其具有治疗潜力。本模型能有效模拟人类疾病进程，为新型治疗方案研究提供了理想平台。

原文链接：

A model of breast cancer meningeal metastases: characterization with in vivo molecular imaging