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In life science research, scientists often aim to learn more about the human body and study how disease affects our bodies. In order to do so, it is necessary to monitor any changes over time. Imaging has a huge potential to allow scientists to do just that.
It is worthwhile to develop, validate and implement 3R methods not only from an ethical point of view, but also for scientific reasons. These alternatives lead to better predictions of the human situation and help to reduce the number of animals involved in testing and the discomfort these animals experience.
Currently, imaging is used in hospitals as a diagnostic tool. Yet imaging is a developing field and has other potential uses as well. At TNO, scientists are investigating how imaging could improve the way animal testing is done.
Imaging allows an animal to be monitored repeatedly. This increases the statistical power of a study and can reduce the number of test animals needed. Since imaging can be used to follow test animals for a period of time, it is possible to monitor the effects of a disease or a treatment through different phases. Another advantage of imaging is that it is usually minimally invasive. This reduces stress and discomfort in test animals, which also benefits the actual study results. There remains much work to be done in order to apply imaging and gain the 3R benefits it may bring. The following examples illustrate the work TNO is performing with imaging.
The goal of this project is to explore PET-CT the use of imaging to measure the activity of the drug transporters BCRP (Breast Cancer Resistance Protein) and P-gp (P-glycoprotein) at the blood-brain barrier in living animals. Both drug transporters play important roles at the blood-brain barrier, where they limit the access of various drugs to the brain. Their functions and activities can be influenced by drugs and they may therefore be involved in so-called drug-drug interactions, in which the inhibition of transporters by one drug increases the brain penetration of another drug. It is therefore very important to investigate whether new drugs can affect the activity of BCRP and/or P-gp at the blood-brain barrier.
TNO has a broad portfolio of disease models with a focus on metabolic diseases (e.g. cardiovascular diseases and diabetes). These models are translational and are therefore very well-suited to unravelling mechanisms in disease processes and evaluating the efficacy of drugs and dietary changes. To increase the translational value of the research, TNO constantly refines the animal models themselves and also aims to mimic the way doctors monitor disease with, for example imaging tools such as MRI.