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3R Compliant Drug Development Studies

In preclinical imaging, magnetic resonance imaging (MRI) can be an attractive alternative to researchers who have previously relied on ultrasound to investigate animal models. Using an ultrasound instrument, animal throughput can be low and operators also need to be highly experienced simply to even find certain organs.

At the Center for Molecular Oncology at Barts Cancer Institute, Queen Mary University of London, researchers have been using preclinical imaging to look at the pharmacokinetics of radiopharmaceuticals, to perform anatomical studies, and to assess treatment responses in mice. The center is fully equipped for radiopharmaceutical development and houses a number of imaging instruments.

One of those instruments is the ICON 1 T MRI from Bruker. In a recent interview, team leader Dr. Jane Sosabowski, explained how the molecular imaging team have been using the ICON to investigate orthotopic pancreatic tumors in mice and described some of the advantages of using this over ultrasound.

The researchers had previously been using ultrasound to investigate these tumors, but preparing the animals and carrying out the imaging had been time consuming. Operators also needed to be highly experienced in ultrasound, even just to find the pancreas, let alone assess any transformation or the extent of that transformation. Almost all of the researchers in the group are biologists who have no background in imaging. The goal therefore became to acquire an instrument that would make things more straightforward for users.

Another goal was to find an instrument with high soft tissue contrast in the abdominal region. A mouse pancreas is a particularly difficult organ to image, explained Sosabowski: “Its shape is defined by the organs around it. We needed something where we would be able to see a difference between the soft tissue of the pancreas, and distinguish that from the intestine in particular, and the spleen and the other tissues that press in on it and define its shape.”

Furthermore, since many orthotopic tumors are buried so deep within the animal, tumor size or shape cannot be assessed and palpitation is very difficult. Sosabowski and team realised they would need to use MRI if they were going to be able to overcome these problems.

Since acquiring the ICON, the team has found implanted pancreatic tumors very easy to see, which allows their imaging to be performed at much shorter scan times.

The ICON has significantly improved animal throughput during experiments, enabling them to get through twice the amount of animals they had previously been able to when using ultrasound. With ultrasound, an experienced operator could get through about ten animals in a day, whereas, now, some users have been able to get through 30 animals in a day.

 

 

 

 

The ICON was part funded by the National Center for the Replacement, Refinement, and Reduction of Animals in Research (NC3Rs). The aim of NC3Rs is that, where animal experiments cannot be replaced by in silico or in vitro methods, then researchers reduce the number of animals being used and also refine their procedures so that animals endure fewer experiments and therefore less suffering.

“The ICON is really good for this,” said Sosabowski “you can do longitudinal imaging, which means you can image the same animal at multiple time points and collect data at those time points, without having to sacrifice any animals at each time point.”

Furthermore, the researchers can start their studies earlier on, since they can see when tumors have reached a suitable size for study. This also means being able to end the study sooner, which is a refinement because the animals suffer less. Tumors never reach a stage where they're too large and the animal endures suffering.

Sosabowski says the center’s records show that multiple animals in multiple studies have been through the ICON and imaged multiple times. This has enabled volumetric data to be obtained, which helps the researchers to see whether a tumor is responding to treatment, shrinking, or just not growing.

When it comes to council funding, scientists are expected to show they have reached the targets set out in their funding application. Since their ICON instrument was funded by NC3Rs, Sosabowski and colleagues wanted to be able to screen animals and measure their responses to therapy using the ICON.

“We have managed to do that,” she concludes.