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Pre-clinical animal models of spontaneous metastatic cancer are infrequent; the few that exist are resource intensive because determination of the presence of metastatic disease, metastatic burden, and response to therapy normally require animal sacrifice and extensive pathological examination. We recently identified and characterized a patient derived xenograft model with metastatic potential, bladder xenograft BL0293-F563, developed by Jackson Laboratories and the University of California at Davis. In this study we performed a detailed imaging characterization of this model, which develops spontaneous liver and bone metastases. Using non-contrast T2 weighted MRI, hepatic metastases were demonstrated 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. T2w turbo spin echo (T2wTSE) sequence was applied in the coronal view with a repetition time (TR) 5333ms, echo time (TE) 65ms, with an in-plane pixel of 0.180 × 0.180 mm2. A Spectral Presaturation with Inversion Recovery (SPIR) sequence (Philips Healthcare, Best, The Netherlands) was used to suppress the fat component and assist in distinguishing fat from cystic mass and tumor tissue. In a group of animals receiving one cycle of effective chemotherapy ([Temozolomide; (50 mg/kg; PO, QDx5)] plus [(veliparib, a poly (ADP-ribose) polymerase inhibitor) (7.75 mg/kg; PO; BIDx7)]), no animals demonstrated metastasis by imaging. The imaging characteristics of this model, which is available from the National Cancer Institute Patient-Derived Models Repository (https://pdmr.cancer.gov/), is highly favorable for preclinical research studies of metastatic disease when used in conjunction with non-contrast T2 weighted MRI.
We would like to thank Nimit Patel of the Small Animal Imaging Program for analyzing ultrasound and assisting with the experiment; Simone Difilippantonio for coordinating her staff and Amy James of the Animal Research Technical Support Program for preparing the drug and administration, measuring body weights, and tumor excision, Laboratory Animal Sciences Program, Frederick National Laboratory for Cancer Research.
This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.