New imaging modality for improved cancer treatment
Cancer is one of the biggest causes of death in Europe, and researchers continue to work on improving diagnosis and treatment. We spoke to Dr Frédéric Lerouge about the work of the SCANnTREAT project in combining a new imaging modality with X-ray activated photodynamic therapy, which could lead to more efficient treatment of cancer.
An imaging modality called SPCCT (spectral photon counting scanner CT) could provide detailed information about a tumour (when using specific contrast media), including its volume and location, information which can then be used to guide cancer treatment. As Principal Investigator of the SCANnTREAT project, Dr Frédéric Lerouge is looking to combine this imaging modality with X-ray activated photodynamic therapy, which will provide a powerful method of treating cancer. “With photodynamic therapy patients are injected with a molecule called a photo-sensitiser, which then goes all over the body. This molecule is sensitive to light at a certain wavelength, for example red light,” he explains. “The idea is that once a patient has ingested this molecule, doctors can conduct an endoscopy for example, and effectively shine a light inside the patient. This red light activates the molecule, which is then lethal to the cancer.”
Photodynamic therapy
This approach is already used to treat certain types of cancer, notably esophagus cancer, yet it has some significant limitations. In particular, photodynamic therapy is not currently effective on tumours located deep within the body, as light can’t reach the photo-sensitiser molecule itself and activate it, an issue that Dr Lerouge and his colleagues in the project are addressing. “We are developing a new strategy to bring light close to a photo-sensitiser molecule and activate it,” he says. This work involves the development of nanoprobes, tiny devices with a diameter of between 9-10 nanometres, which generate reactive oxygen species under low energy x-ray irradiation. “When we shine x-rays on the nanoprobes they in turn emit light, which can then be re-absorbed by the photo-sensitiser,” continues Dr Lerouge. “This is related to a mechanism called scintillation.”
The ability to activate the photo-sensitiser molecule in a controlled way, and to turn it on and off at will, opens up the possibility of targeting cancer treatment more precisely than is currently possible. One
approach commonly used to treat cancer is radiotherapy, where high-energy x-rays are shone directly on a tumour to destroy it, yet Dr Lerouge says this also leads to
to image a tumour with the scanner and treat it afterwards, we will therefore be able to reduce side-effects and improve treatment efficiency,” says Dr Lerouge.
“With photodynamic therapy patients are injected with a molecule called a photo-sensitiser, which then goes all over the body. This molecule is sensitive to light at a certain wavelength, for example red light.”
side-effects. “Radiotherapy can destroy a tumour, but it may also destroy surrounding healthy tissue, which can lead to various side effects,” he outlines. The new approach to treatment that researchers are developing in the project is designed to have less complications. “Indeed, with the nanoprobes designed during the project it will be possible
A more precise and targeted method of treating cancer could also reduce the likelihood of a recurrence of the disease, which is a major concern. Even if a cancer is treated successfully with current methods, some cancerous cells may be left in the body, which leaves people vulnerable. “These cancerous cells may effectively lie dormant for a time,
but they can lead to the development of a tumour in future. If all of the cancer cells can be eradicated, this could prevent the recurrence of the disease,” explains Dr Lerouge.
Photodynamic therapy is already used in cancer treatment, now Dr Lerouge is exploring the possibility of widening its use, particularly in treating pancreatic cancer, which is typically diagnosed at quite a late stage. “The aim would be to provide an effective and efficient treatment method,” he says.
Researchers in the project are currently conducting tests on mice, which are both imaged with a conventional scanner, and also imaged with the SPCCT modality following injection with the nanoprobes. “When you use this specific imaging technique you can choose to see only the areas where the nanoprobes are located, which gives us a very accurate diagnosis,” explains Dr Lerouge.
“When you merge the two images it gives you a more precise picture of where the nanoprobes are, that can then be used to guide treatment. We’re interested not just in improving diagnosis, but also in monitoring the pathology during treatment.”
This will allow clinicians to assess the effectiveness of treatment, and if necessary adapt it to reflect the degree of progress that
has been made. If everything is going well, and the patient is responding positively to treatment, then it might be possible to reduce the dose of x-rays to be delivered for example, or the opposite might be the case. “If we see that things aren’t going our way we can choose to increase the x-rays a little bit. The main consideration is always the wellbeing
of the patient,” stresses Dr Lerouge. The information gained in the process can then be very useful in guiding the treatment of other patients in future. “We want to provide this information in databases to help improve treatment as much as possible, from the very early stages when the pathology is initially diagnosed,” continues Dr Lerouge.
Part of the members of the consortium of the SCANnTREAT project around the spectral scanner.
SCANnTREAT
Photodynamic therapy triggered by spectral scanner CT: an efficient tool for cancer treatment
Project Objectives
The projects aims at combining two cuttingedge technologies for the treatment of cancer : spectral photon counting scanner CT a ground-breaking imaging modality and a new treatment known as X-rays activated Photodynamic Therapy (X-PDT). The perfect match between these two technologies is ensured with specifically designed probes acting both as contrast media and therapeutic agents.
Project Funding
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 899549.
Project Consortium
• The University Claude Bernard Lyon 1 (UCBL) - Chemistry Laboratory
• The University Claude Bernard Lyon 1 (UCBL) - CREATIS
• Inserm UA7 unit Synchrotron Radiation for Biomedicine (STROBE)
• Inserm The UA8 Unit “Radiations: Defense, Health and Environment”
• Maastricht University (UM) - D-Lab
• Philips Medical Systems Technologies, Ltd., Israel (PMSTL)
• Lyon Ingénierie Projets https://www.scanntreat.eu/governance.html
Contact Details
Project Coordinator, Dr Frederic Lerouge
Chemistry Laboratory
UMR 5182 ENS/CNRS/University claude bernard Lyon 1
9 Rue du Vercors
69007 Lyon
T: +33 6 14 14 50 86
E: Frederic.lerouge@univ-lyon1.fr
W: https://www.scanntreat.eu/
Dr Frederic Lerouge is assistant professor at the Claude Bernard Lyon 1 University, a position he has held since 2007. His main research interests focus on the design of inorganic nanomaterials and their surface modifications for applications in health and environment.
Animal models
A major next step for Dr Lerouge and his colleagues will be to test the technology on a broader range of small animal models, gaining deeper insights into its overall effectiveness and identifying any ways in which it could be improved. This work is still at a relatively early stage however, and Dr Lerouge plans to establish a successor project beyond the conclusion of SCANnTREAT later this Summer, in which he intends to pursue further research. “We need to do some more work and gather more data. We also have ideas about how to develop the technology, which will evolve depending on the results of our research, in terms of the quality of diagnosis and efficiency of treatment,” he continues. “We are looking to improve the technology, and to ensure that we will be able to actually use this system.”
The long-term vision is to use this technology to treat cancer in human patients, and with healthcare budgets under strain, costeffectiveness is an important consideration. The SCANnTREAT system itself is expensive, the result of dedicated work in the laboratory, yet Dr Lerouge believes it can lead to financial benefits over the long-term by reducing the need for further action following treatment, which currently is a major cost in cancer care. “Some patients are treated for cancer, but they remain in a fragile state and they are not restored to full health. They may then need further treatment for other conditions,” he explains. “The idea is that once this treatment has been administered it is over, and the patient can then get back to normal life. This is one of the issues that people who work on cancer treatment look at very closely.”
The project’s research represents an important contribution in this respect, and in future Dr Lerouge plans to build on the progress made in SCANnTREAT, and move the new treatment closer to practical application.
“We are looking to establish a new consortium, to push this technology forward and to test it on different cancer models,” he says. Researchers hope to probe the limits of this technology, and also to look at how it can be improved further. “We intend to look at what we can achieve in terms of the efficiency of treatment, and also at what kinds of cancer we could treat with this approach,”
The ultimate goal is to develop a new method of treating cancer that can be administered to human patients. “We hope to treat human patients with this technology within the next five years or so,” says Dr Lerouge.
Dr Frederic Lerouge
3D structure of a melanoma cell derived by ion abrasion scanning electron microscopy. Image by National Cancer Institute
Electronic microscopy photo of the nanoprobes used during the SCANnTREAT project, average sizes are below 10 nm.