Between Prometheus and Thanatos: Reflections on Intracardiac Injection Models for Metastasis in Mice

Intracardiac injection is a commonly used method to establish experimental metastases in mice, particularly in models of breast and prostate cancer. This technique enables rapid dissemination of tumor cells to the skeleton and brain but carries significant animal welfare concerns due to high rates of morbidity, including paralysis, weight loss, and multiorgan failure. This narrative review evaluates the welfare implications of the intracardiac model, synthesizing data from preclinical studies. Alternative techniques, such as intratibial, caudal artery, intracarotid, and intracranial injection, are compared in terms of procedural refinement, disease localization, survival time, and humane endpoints. These methods offer improvements in reproducibility and welfare while maintaining relevance to metastasis research. We discuss how these refinements can reduce animal burden and improve model selection in line with the 3Rs (Replacement, Reduction, and Refinement).