In oncology research, while xenograft tumor models are easily visualized and humane endpoints can be clearly defined, metastatic tumor models are often based on more subjective clinical observations as endpoints. This study aimed at identifying objective non-invasive criteria for predicting imminent distress and mortality in metastatic lung tumor-bearing mice. BALB/c and C57BL/6 mice were inoculated with CT26 or B16F10 cells, respectively. The mice were housed in Vium smart cages to continuously monitor and stream respiratory rate and locomotion for up to 28 days until scheduled euthanasia or humane endpoint criteria were met. Body weight and body temperature were measured during the study. On days 11, 14, 17 and 28, lungs of subsets of animals were microCT imaged in vivo to assess lung metastasis progression and then euthanized for lung microscopic evaluations. Beginning at day 21, most tumor-bearing animals developed increased respiratory rates followed by decreased locomotion 1-2 days later, compared with the baseline values. Increases in respiratory rate did not correlate to surface tumor nodule counts or lung weight. Body weight measurement did not show significant changes from days 14-28 in either tumor-bearing or control animals. We propose that increases in respiratory rate (1.3-1.5 X) can be used to provide an objective benchmark to signal the need for increased clinical observations or euthanasia. Adoption of this novel humane endpoint criterion would allow investigators time to collect tissue samples prior to spontaneous morbidity or death and significantly reduce the distress of mice in the terminal stages of these metastatic lung tumor models.

中文翻译：

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自动监测呼吸频率作为一种新颖的人道终点：小鼠转移性肺癌模型的改进。


在肿瘤学研究中，虽然异种移植肿瘤模型很容易可视化并且可以清楚地定义人道终点，但转移性肿瘤模型通常基于更主观的临床观察作为终点。本研究旨在确定客观的非侵入性标准来预测转移性肺肿瘤小鼠即将面临的痛苦和死亡率。 BALB/c和C57BL/6小鼠分别接种CT26或B16F10细胞。这些小鼠被安置在 Vium 智能笼中，持续监测和记录呼吸频率和运动长达 28 天，直到达到预定的安乐死或人道终点标准。研究期间测量了体重和体温。在第 11、14、17 和 28 天，对部分动物的肺部进行体内 microCT 成像，以评估肺转移进展，然后实施安乐死以进行肺部显微镜评估。从第 21 天开始，与基线值相比，大多数荷瘤动物的呼吸频率增加，随后 1-2 天后运动减少。呼吸频率的增加与表面肿瘤结节计数或肺重量无关。从第 14 天到第 28 天，荷瘤动物或对照动物的体重测量没有显示出显着变化。我们建议呼吸频率的增加（1.3-1.5 X）可用于提供客观基准，以表明需要增加临床观察或安乐死。采用这种新颖的人道终点标准将使研究人员有时间在自发发病或死亡之前收集组织样本，并显着减少这些转移性肺肿瘤模型末期小鼠的痛苦。