Abstract
An increasing volume of pre-clinical and clinical-translational research is attempting to identify novel biomarkers for improved diagnosis and risk-stratification of chemotherapy-induced cardiotoxicity. Most published animal models have employed weekly intraperitoneal injections of doxorubicin to reach a desired cumulative dose. This approach can be associated with severe systemic toxicity which limits the animal model usefulness, particularly for advanced imaging. In the current study, slow-release subcutaneous doxorubicin pellets demonstrated histopathologic evidence of cardiotoxicity at doses similar to standard human dose-equivalents without limiting animal survival or ability to participate in advanced imaging studies. This approach may provide a more robust cardiotoxicity animal model.
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Abbreviations
- CMR:
-
Cardiac magnetic resonance imaging
- PET:
-
Positron emission tomography
- IP:
-
Intraperitoneal
- TUNEL:
-
Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling
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Acknowledgements
This work was supported by Northwestern University’s Center for Advanced Microscopy and a Cancer Center Support Grant (NCI CA060553). Histology services were provided by the Northwestern University Mouse Histology and Phenotyping Laboratory which is supported by NCI P30-CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center. The authors also acknowledge Quanhong Grace Ma, Research Lab Manager, Northwestern University Department of Radiology for her contributions to this project.
Funding
This work was funded by an RSNA Resident Research Grant (RR1602).
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JCC has a research relationship with Siemens, and reports travel/accommodations expenses reimbursed by Siemens. All additional authors have no disclosures.
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Allen, B.D., Zhang, Z., Naresh, N.K. et al. Slow-Release Doxorubicin Pellets Generate Myocardial Cardiotoxic Changes in Mice Without Significant Systemic Toxicity. Cardiovasc Toxicol 19, 482–484 (2019). https://doi.org/10.1007/s12012-019-09521-0
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DOI: https://doi.org/10.1007/s12012-019-09521-0