PENNINCKX Sebastien

Units

The research activities of our laboratory, combining clinical and fundamental research, are developed as part of multidisciplinary approaches and in close collaboration with the departments of Nuclear Medicine, Radiology and Radiotherapy. Thanks to the different expertise of our researchers and our intrinsic collaborations, our research topics are highly diversified.
One of our principal research fields concerns the development of data sciences, including artificial intelligence techniques. Our goal is to develop predictive and prognostic models for internal and external radiotherapy treatments, and on a broader level of Oncology treatments. Biomarkers are extracted from perfusion CT, functional MRI and metabolic/molecular (SPECT and PET) images using Radiomics analysis, possibly combined with biomarkers coming from Genomics, Proteomics, etc. This research topic is of particular interest for the concomitant development of the MRI-Linac and the Theranostic agents (e.g. 68-Gallium/177-Lutetium PRRT and PSMA, etc.). Optimal cancer care needs a holistic view of the patient and the disease and the development of such predictive and prognostic models are deemed essential for improving patient selection and the guidance of their treatment plan.
Another important aspect of our research is the optimization of radiotherapy techniques, notably using artificial intelligence for automatic image delineation (CT, MRI and PET images), absorbed-dose prediction, generation of pseudo-CT from MRI images and TCP/NTCP modelling. This research pillar also focuses on integrating multimodality imaging as part of precision radiotherapy approaches (MRI guided robotic brachytherapy, MRI guided Gammaknife, Theranostics dosimetry, etc).
Moreover our laboratory has research projects in 3D printing, in radiobiology (collaborations with the BRTP: Brussels RadioTheragnostic Platform and the PIRaTH: Preclinical imaging and radiation therapy platform) and on the combination of radiotherapy techniques with immunotherapy. Last but not least, we are participating in the research activities of future proton therapy facilities in Charleroi.

Projetcs

Flash or not FLASH ?

Radiotherapy has not stopped evolving since the last century. From the increase in photon energy to the emergence of heavy particles, treatments have become more and more conformal. These improvements have led to greater outcomes and reduced toxicity (1). Recently, following pre-clinical trials (2) (3) (4) and treatment of the first human patient (5), Flash radiotherapy (Ultra-short pulsed high dose rate radiation therapy) has created a ripple effect in the radiation therapy community (6). Strikingly, these studies reported a significant decrease in toxicity, whereof the mechanism is still not fully understood, while maintaining efficient anti-tumor activity. If these results could be confirmed by other studies on humans this would cause a genuine revolution in the field. In this dose-escalation study we plan to irradiate symptomatic superficial or cutaneous lesions. In the preclinical part of this project, we aim to unravel the exact mechanisms underlying FLASH-RT effect.

Dosimetry for Carbon, ARC and FLASH therapies: D-CAF: MecaTech

- 	Proton ARC therapy will require detectors that must follow in real time the gantry motion, which is not a feature of the current IBA Dosimetry equipment. 
-	Carbon ion therapy will require specific investigations to understand perturbation effect of nuclear interactions to develop a compatible dosimetry equipment which will not be affected by them

Development of personalized neutron capture therapy using theranostic carriers

Boron neutron capture therapy (BNCT) is an emerging radiation therapy based on the interaction between a
non-radioactive boron-10 labelled compound and low-energy thermal neutrons. This interaction leads to the
production of α-particles, known to be more effective in inducing cell death than conventional X-rays. Due to
their short range in tissue, the induced cell damage remains confined to cells containing boron atoms. Thus,
BNCT has the potential to revolutionize radiation oncology by positioning itself as a selective and targeted
radiotherapy. However, the concentration of boron in the tissue cannot be determined at irradiation time,
limiting the optimal use of this technology in the clinic.
In this project, we propose to modify BPA, a clinically approved boron-compound by grafting MRI contrast
agents (157Gd and 19F) onto it. This creates a theragnostic vector that opens the door to personalized
medicine in BNCT. We will study the toxicity and internalization of our compounds in in vitro systems.
Intracellular microdistribution of these compounds will be implemented in Monte Carlo codes to predict the
influence of each compound on the delivered dose. The biodistribution kinetics of the compounds and their
accumulation in the target tissues will be studied in murine models already available in the laboratory. The
obtained MRI images will be used for the implementation of a personalized treatment plan that will guide
irradiation experiments. Irradiation of our biological systems will be performed to evaluate tumor control,
additive or synergistic effect of Gd or F moities and the radiobiological responses (DNA damages, ...) using
cellular and molecular biology analyses. Finally, the damage to healthy tissues will be assessed by ex-vivo
histological analyses.
All the information collected will lay the foundation for clinical trials that will start at the end of this project.

Development of personalized neutron capture therapy using theranostic carriers