3D phantom models that mimic optical and physical properties of tumours can be used as an alternative to animal experiments when testing surgical imaging technologies. The models are printed in various shapes of real tumours, are a few centimetres in size and are composed of substances such as lipids, haemoglobin, enzymes and tumour cells bound with gelatine.
The models were developed under the guidance of Indrajit Srivastava, assistant professor of mechanical engineering at Texas Tech University. Srivastava was looking for a reliable way to test an imaging technology called afterglow imaging. This is an alternative to fluorescence imaging-based surgery, where light penetrates deeper into tumours and remains visible for longer. Importantly, this gives surgeons more time to remove tumours as accurately as possible.
Afterglow imaging is therefore seen as a promising imaging technology. However, before it can be widely used, more research is needed. Normally, this research takes place using animal experiments. However, Srivastava points out that tests on mice are unreliable due to differences in skin and tissues of humans and mice.
'Mice are not the best model for these studies'
"As you might expect, the skin of mice is very thin - just a few millimetres - whereas in humans it is very different because we have layers of fat, muscle and tissues that can actually affect the performance of the imaging agent," Srivastava explains. "So mice are actually not the best model for these studies."
New 3D models could be the answer. They include all the elements present in human tumours and therefore accurately mimic the tumours. This allows tests to be carried out as realistically as possible. At the same time, fewer animal tests are needed.
Much cheaper alternative than animal testing
"When a nanoparticle or imaging agent passes through the artificial tumour, it can mimic that environment and the optical signals will be affected as in human patients," reports Srivastava. "This is a much cheaper alternative than animal testing because you can do it more often to get statistical significance."
Led by Srivastava, the models were developed by Asma Harun, a PhD student in mechanical engineering, and Nate Bendele, a former biochemistry student. Other members of the lab involved in the research are student researchers in biochemistry Isabella Vasquez and Jonathan Djuanda, as well as PhD student in mechanical engineering Hasnat Rashid. The project also included collaborations with other labs at Texas Tech University and the Texas Tech University Health Sciences Center.
Quest for a better binder
The team collected data for a year and a half using the models. Based on this, the researchers published a paper in American Chemical Society, ACS Nano. Currently, Srivastava is searching for a binder that outperforms gelatine and can handle temperature fluctuations while shipping the models.
Srivastava also wants to develop a way to keep tumour cells alive longer in the 3D phantom models. "Once these cells are in the phantom model, they slowly start to die," Srivastava explains. "What we are trying to do is to have a phantom in which the tumour cells inside stay alive for weeks. Then you are actually trying to image a live tumour and that gives you more optical information that can be useful to a surgeon."
'I think people have overused mouse studies'
Srivastava points out that the US Food and Drugs Administration (FDA) is increasingly focusing on human-centred research. He expects 3D phantom models to play an important role in this. "I think humans have overused mouse studies, at least from the point of view of showing their nanoprobes for surgery," says assistant professor.
"Ultimately, the main priority should be how close the work is to actual clinical use. I think in cases like surgical navigation, my studies are more human-centred because we are trying to address the optical challenges that these imaging tools are exposed to. We actually take into account how this technology would behave when you use it in an operating theatre."
