BACKGROUND Spontaneously metastatic xenograft models of cancer are infrequent and the few that exist are resource intensive. In xenografts, caliper measurements can be used to determine primary tumor burden and response to therapy but in metastatic disease models determination of the presence of metastatic disease, metastatic burden, and response to therapy are difficult, often requiring serial necropsy. In this study we characterized the development of visceral metastases in a patient derived xenograft model (PDXM) using in vivo imaging. RESULTS We identified and characterized the previously unreported development of spontaneous liver and bone metastasis in a known patient derived xenograft, bladder xenograft BL0293F, developed by Jackson Laboratories and the University of California at Davis and available from the National Cancer Institute Patient-Derived Models Repository [1]. Among FDG-PET/CT, contrast-enhanced MRI and non-contrast MRI, non-contrast T2w MRI was the most effective and efficient imaging technique. On non-contrast T2 weighted MRI, hepatic metastases were observed in over 70% of animals at 52 days post tumor implantation without resection of the xenograft and in 100% of animals at day 52 following resection of the xenograft. In a group of animals receiving one cycle of effective chemotherapy, no animals demonstrated metastasis by imaging, confirming the utility of this model for therapy evaluation. There was good agreement between pathologic grade and extent of involvement observed on MRI T2w imaging. CONCLUSION PDX BL0293F is a reliable visceral organ (liver) metastatic model with high penetrance in both non-aggravated and post excisional situations, providing a reliable window for therapy intervention prior to required excision of the xenograft. The imaging characteristics of this model are highly favorable for non-clinical research studies of metastatic disease when used in conjunction with non-contrast T2 weighted MRI.

中文翻译：

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膀胱癌的自发转移模型：影像学表征。

背景技术癌症的自发转移性异种移植模型很少见，并且存在的少数模型是资源密集型的。在异种移植物中，卡尺测量可用于确定原发性肿瘤负荷和对治疗的反应，但在转移性疾病模型中，确定转移性疾病，转移性负荷和对治疗的反应存在困难，通常需要进行尸检。在这项研究中，我们表征了使用体内成像的患者衍生异种移植模型（PDXM）中内脏转移的发展。结果我们确定并表征了先前已知的患者自体异种移植物，膀胱异种移植物BL0293F自发性肝和骨转移的发展，由杰克逊实验室和加州大学戴维斯分校开发，可从美国国家癌症研究所患者衍生模型库中获得[1]。在FDG-PET / CT，对比增强MRI和非对比MRI中，非对比T2w MRI是最有效和高效的成像技术。在非对比T2加权MRI上，在未植入异种移植物的肿瘤植入后52天，超过70％的动物观察到肝转移，而在异种移植物切除后52天，在100％的动物中观察到肝转移。在接受一个有效化疗周期的一组动物中，没有动物通过成像显示出转移，证实了该模型在治疗评估中的实用性。在MRI T2w成像上观察到的病理分级和受累程度之间有很好的一致性。结论PDX BL0293F是一种可靠的内脏器官（肝）转移模型，在非加重和切除后情况下均具有较高的穿透性，为在需要切除异种移植物之前进行治疗干预提供了可靠的窗口。当与非对比T2加权MRI结合使用时，该模型的成像特性对于转移性疾病的非临床研究非常有利。