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Photodynamic therapy triggered by spectral scanner CT: an efficient tool for cancer treatment

Periodic Reporting for period 2 - SCANnTREAT (Photodynamic therapy triggered by spectral scanner CT: an efficient tool for cancer treatment)

Reporting period: 2021-09-01 to 2022-08-31

According to Eurostat, cancer accounts for the second cause of death in Europe and represents a 25% share of the worldwide cancer burden, despite the fact that Europe represents only 9% of the world population. Numerous treatment strategies exist: surgery, chemotherapy or radiation therapy, but outcomes are not always successful. Furthermore, even if in some cases five-year survival post treatment can be encouraging, the conditions of life of the patients are deteriorated due to side effects of the therapies.
We are aiming at a breakthrough technology that will contribute to increase drastically patients five years survival and have significant positive impact on their quality of life. Such ambition will be reached thanks to a new future technology that will ensure the efficient treatment of cancer, even if radioresistant, with low side effects, allow to perform accurate diagnostic and give access to in situ monitoring of the treatment. The other ground-breaking aspect of this technology is the fact that everything will take place at the same time, with the same machine which will be much less stressful and disturbing for patients compared to other treatment. This technology will have a knock-on effect on European healthcare systems’s expenses associated to cancer treatment and post-treatment.
SCANnTREAT is the starting point of that ambition, it is based on the association of cutting-edge technologies: spectral photon counting scanner CT (SPCCT) which is a ground-breaking imaging modality and a new X-ray based treatment known as X-rays activated Photodynamic Therapy (X-PDT). The perfect match between these two technologies will be ensured with specifically designed probes acting both as contrast media and therapeutic agents
During the first year of the project, efforts were made in the design of scintillating nanoparticles, surface modification to ensure their biocompatibility and in vitro evaluation of their internalization/toxicity.
- Inorganic nanoparticles doped with various mount of Terbium were prepared and the optimized composition was set based on emission properties of the probes. The particles have a diameter below 10 nm evaluated by TEM and show highly crystalline orthorhombic structure.
- Thorough study of the scintillation (ie emission of light upon excitation by X-rays) properties was performed with mircoCT device. The nanoparticles show intense emission in the green, corresponding to the emission of Terbium.
- The functionalization of the particle was conducted with a series of molecules and macromolecules such as polyethylene glycol derivatives or albumin. Also, core-shell systems were considered with a layer of silica surrounding the nanoparticles. The obtained hybrid systems were analyzed with several techniques (Dynamic Light Scattering, Infrared, Thermogravimetric analysis, ICP…etc) to prove the efficient surface modification. All prepared probes are stable in saline media such as PBS buffer making them suitable for further in vitro studies.
- The kinetics of intracellular diffusion of the probes was studied on healthy and cancer cell lines. Synchrotron X-rays fluorescence microscopy was used to study the internalization of the probes. Several concentrations of nanoparticles suspensions were incubated with cells during 24 hours before imaging. Results first show no toxicity of the probes whatever the concentration considered. Imaging clearly evidenced the colocalization of endosomes and main elements of the probes.

The specific objectives for the second period were (a) the finalization on the work of scintillation quantification under X-rays, (b) the surface modification of the nanoparticles with various systems, (c) characterizations of effective surface modification and (d) preliminary work on generation of ROS.
Our ambition is to improve cancer treatment and to translate fundamental research discoveries into medical applications, health benefit and value for European society. In parallel to the novelty of the physical and technical features and the clinical potential approach, we will strive to reinforce the development of this new technology by a very rigorous and innovative radiobiological study to secure its clinical transfer by optimising its anti-cancer efficiency while preventing radiosensitivity reactions on healthy tissues. Finally, our vision is to lay the foundations for radically new future technologies and to encourage the driving role of new actors in research and innovation, giving great opportunities to ensure the European partners leadership on further developments for the next decade.
SCANnTREAT will contribute to the sustainability of health care systems and healthcare costs through reduced treatment time, better recovery (compared to Radiotherapy). Better evaluation and treatment of cancer patients are anticipated to lower mortality and improve their quality of life. Finally, since scanner CT are commonly used across EU this new treatment will be accessible throughout all Europe.