蛛网膜下转移是乳腺癌的致命并发症，当癌细胞在蛛网膜中生长时，会引起此病。目前尚无治愈方法，患者的生存期少于四个月。治疗选项为姑息性治疗。我们就此研究了一种可复制的条件性疱疹病毒HSV1，并呈现了此种溶瘤性HSV1在不同阶段的乳腺癌蛛网膜下转移的治疗疗效，分别是滞后期、中间期和指数期的生长。 在小鼠模型中，这些阶段代表了患者蛛网膜疾病的早期，中期和晚期。在该模型中，病毒通过立体定向手术送入脑室系统，就像引入癌细胞以创建蛛网膜下转移一样。 使用Gd-MRI测量肿瘤生长，通过FHBG-PET和Fluc生物发光来评估病毒复制情况。成像结果与H&E和HSV-TK免疫组织化学染色相对应。 观察到当滞后期被靶向时，发生了显着的生长抑制，与多次病毒复制周期有关。疾病的发作被延迟，生存期延长了近两个星期。靶向中间期时，观察到与强大的病毒复制相关的类似滞后期的生长抑制。现有肿瘤的回归导致神经症状逆转，并将生存期延长近一周。当靶向滞后期时，观察到较小的反应，生存期延长3天。溶瘤性HSV1提供了一种新的治疗选择，用于治疗乳腺癌蛛网膜下转移，并具有针对不同疾病阶段的潜力，其中病毒复制和肿瘤反应可以使用临床上的分子成像技术进行监测。 © 2023。作者（们）独家授权给Springer Nature America，Inc。

Leptomeningeal metastasis is a fatal complication of breast cancer which results when cancer cells seed in the meninges. Currently there is no cure, limiting survival to less than four months. Treatment options are palliative. We studied a replication conditional Herpes simplex virus 1 (HSV1) in this regard and present the therapeutic efficacy of oncolytic HSV1 on different stages of breast cancer leptomeningeal metastases growth, namely the lag, intermediate, and exponential phases. These phases characterized in a murine model represent the early, intermediate, and late stages of leptomeningeal disease in patients. In this model, virus was introduced into the ventricular system by stereotactic surgery, the same path cancer cells were introduced to create leptomeningeal metastases. Tumor growth was measured with Gd-MRI and virus replication was assessed by FHBG-PET and Fluc bioluminescence. Imaging results were correlated with H&E and HSV-TK immunohistochemical staining. A remarkable growth inhibition was observed when the lag phase was targeted which was associated with multiple virus replication cycles. The onset of debilitating symptoms was delayed, and survival was lengthened by nearly 2 weeks. A growth inhibition similar to the lag phase was observed when the intermediate phase was targeted, associated with robust virus replication. The regression of existing tumor led to a reversal of neurological symptoms, extending survival by nearly one week. A modest response was observed when the lag phase was targeted lengthening survival by 3 days. Oncolytic HSV1 presents a novel treatment option for breast cancer leptomeningeal metastases with potential for targeting different disease stages where virus replication and tumor response can be monitored with molecular imaging techniques that are in the clinic.© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.