Obrecht Michael, Zurbruegg Stefan, Accart Nathalie, Lambert Christian, Doelemeyer Arno, Ledermann Birgit, Beckmann Nicolau
Diseases of Aging and Regenerative Medicines, Novartis Institutes for BioMedical Research, Basel, Switzerland.
Neurosciences Department, Novartis Institutes for BioMedical Research, Basel, Switzerland.
Front Pharmacol. 2023 Jun 28;14:1177421. doi: 10.3389/fphar.2023.1177421. eCollection 2023.
The 3Rs principles-reduction, refinement, replacement-are at the core of preclinical research within drug discovery, which still relies to a great extent on the availability of models of disease in animals. Minimizing their distress, reducing their number as well as searching for means to replace them in experimental studies are constant objectives in this area. Due to its non-invasive character imaging supports these efforts by enabling repeated longitudinal assessments in each animal which serves as its own control, thereby enabling to reduce considerably the animal utilization in the experiments. The repetitive monitoring of pathology progression and the effects of therapy becomes feasible by assessment of quantitative biomarkers. Moreover, imaging has translational prospects by facilitating the comparison of studies performed in small rodents and humans. Also, learnings from the clinic may be potentially back-translated to preclinical settings and therefore contribute to refining animal investigations. By concentrating on activities around the application of magnetic resonance imaging (MRI) and ultrasound elastography to small rodent models of disease, we aim to illustrate how imaging contributes primarily to reduction and refinement in the context of pharmacological research.
3R原则——减少、优化、替代——是药物发现临床前研究的核心,而药物发现仍在很大程度上依赖于动物疾病模型的可用性。尽量减少动物痛苦、减少动物数量以及在实验研究中寻找替代动物的方法是该领域的长期目标。由于其非侵入性特点,成像通过对每只动物进行重复的纵向评估(动物自身作为对照)来支持这些努力,从而能够大幅减少实验中的动物使用量。通过评估定量生物标志物,对病理进展和治疗效果进行重复监测变得可行。此外,成像具有转化前景,有助于比较在小型啮齿动物和人类身上进行的研究。而且,从临床获得的经验可能会潜在地反向应用于临床前研究,从而有助于完善动物研究。通过专注于将磁共振成像(MRI)和超声弹性成像应用于小型啮齿动物疾病模型的相关活动,我们旨在说明成像在药理学研究背景下如何主要有助于减少和优化。