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Establishment and Image based evaluation of a New Preclinical Rat Model of Osteoblastic Bone Metastases

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Abstract

Bone remodeling is disrupted in the presence of metastases and can present as osteolytic, osteoblastic or a mixture of the two. Established rat models of osteolytic and mixed metastases have been identified changes in structural and tissue-level properties of bone. The aim of this work was to establish a preclinical rat model of osteoblastic metastases and characterize bone quality changes through image-based evaluation. Female athymic rats (n = 22) were inoculated with human breast cancer cells ZR-75-1 and tumor development tracked over 3–4 months with bioluminescence and in-vivo µCT imaging. Bone tissue-level stereological features were quantified on ex-vivo µCT imaging. Histopathology verified the presence of osteoblastic bone. Bone mineral density distribution was assessed via backscattered electron microscopy. Newly formed osteoblastic bone was associated with reduced mineral content and increased heterogeneity leading to an overall degraded bone quality. Characterizing changes in osteoblastic bone properties is relevant to pre-clinical therapeutic testing and treatment planning.

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Acknowledgements

Canadian Institute of Health Research (#156175), Ontario Graduate Scholarship in Science and Technology (OGSST).

Funding

Canadian Institute of Health Research (#156175), Ontario Graduate Scholarship in Science and Technology (OGSST).

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Authors and Affiliations

  1. Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada

    Soroush Ghomashchi & Margarete K. Akens

  2. Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada

    Allison Clement

  3. Sunnybrook Research Institute, Toronto, ON, Canada

    Cari M. Whyne

  4. Department of Surgery, University of Toronto, 101 College Street, Rm 15-311, M5G 1L7, Toronto, ON, Canada

    Cari M. Whyne & Margarete K. Akens

  5. Techna Institute, University Health Network, 101 College Street, Rm 15-311, M5G 1L7, Toronto, ON, Canada

    Margarete K. Akens

Authors
  1. Soroush Ghomashchi
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  2. Allison Clement
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  3. Cari M. Whyne
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  4. Margarete K. Akens
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Correspondence to Margarete K. Akens.

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Institutional ethics approval was obtained for all animal experiments and the ARRIVE guidelines were followed.

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Ghomashchi, S., Clement, A., Whyne, C.M. et al. Establishment and Image based evaluation of a New Preclinical Rat Model of Osteoblastic Bone Metastases. Clin Exp Metastasis 39, 833–840 (2022). https://doi.org/10.1007/s10585-022-10175-6

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  • DOI: https://doi.org/10.1007/s10585-022-10175-6

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