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Murine liver implantation of radiation-induced fibrosarcoma: characterization with MR imaging, microangiography and histopathology

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Abstract

We sought to establish and characterize a mouse liver tumor model as a platform for preclinical assessment of new diagnostics and therapeutics. Radiation-induced fibrosarcoma (RIF-1) was intrahepatically implanted in 27 C3H/Km mice. Serial in vivo magnetic resonance imaging (MRI) with a clinical 1.5-T-magnet was performed using T1- (T1WI), T2- (T2WI), and diffusion-weighted sequences (DWI), dynamic contrast-enhanced MRI (DCE-MRI), and contrast-enhanced T1WI, and validated with postmortem microangiography and histopathology. Implantation procedure succeeded in 25 mice with 2 deaths from overdosed anesthesia or hypothermia. RIF-1 grew in 21 mice with volume doubling time of 2.55±0.88 days and final size of 216.2±150.4 mm3 at day 14. Three mice were found without tumor growth and one only with abdominal seeding. The intrahepatic RIF-1 was hypervascularized with negligible necrosis as shown on MRI, microangiography and histology. On DCE-MRI, maximal initial slope of contrast-time curve and volume transfer constant per unit volume of tissue, K, differed between the tumor and liver with only the former significantly lower in the tumor than in the liver (P<0.05). Liver implantation of RIF-1 in mice proves a feasible and reproducible model and appears promising for use to screen new diagnostics and therapeutics under noninvasive monitoring even with a clinical MRI system.

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Acknowledgements

This work was partially supported by the grants awarded by Fonds voor Wetenschappelijk Onderzoek-Vlaanderen (FWO Vlaanderen) Impulsfinanciering project (ZWAP/05/018), Geconcerteerde Onderzoeksactie (GOA) of the Flemish Government, OT project (OT/06/70) MoSAIC, the K.U. Leuven Molecular Small Animal Imaging Center (KUL EF/05/08), and a EU project Asia-Link CfP 2006- EuropeAid/123738/C/ACT/Multi–proposal no. 128–498/111.

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Authors and Affiliations

  1. Department of Radiology, University Hospitals, Catholic University of Leuven, Herestraat 49, 3000, Leuven, Belgium

    Huaijun Wang, Feng Chen, Frederik De Keyzer, Lixin Jin, Jie Yu, Guy Marchal & Yicheng Ni

  2. Laboratory for Pharmaceutical Biology, Faculty of Pharmaceutical Sciences, K.U. Leuven, Herestraat 49, 3000, Leuven, Belgium

    Marie Van de Putte & Peter de Witte

  3. Department of Radiology, Zhong Da Hospital, Southeast University, 87 Ding Jia Qiao Road, Nanjing, 210009, Jiangsu Province, China

    Feng Chen

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  1. Huaijun Wang
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  2. Marie Van de Putte
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  3. Feng Chen
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  4. Frederik De Keyzer
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  5. Lixin Jin
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  6. Jie Yu
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  7. Guy Marchal
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  8. Peter de Witte
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  9. Yicheng Ni
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Correspondence to Yicheng Ni.

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Wang, H., Van de Putte, M., Chen, F. et al. Murine liver implantation of radiation-induced fibrosarcoma: characterization with MR imaging, microangiography and histopathology. Eur Radiol 18, 1422–1430 (2008). https://doi.org/10.1007/s00330-008-0904-2

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  • DOI: https://doi.org/10.1007/s00330-008-0904-2

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