Preclinical Radiobiology
In the field of oncology, the use of ionizing radiation is akin to a complex ballistic exercise. Our primary aim is to deposit the therapeutic dose precisely within the tumor volume of interest while minimizing the impact on surrounding healthy tissues. Currently, the dose received by these healthy tissues remains a limiting factor in the efficacy of radiotherapy treatments, as it triggers the induction of adverse effects for patients. Within our research group, we are dedicated to enhancing radiotherapy treatments by optimizing the therapeutic window via a reduction of normal tissue complication. To achieve this goal, we undertake a comprehensive and interdisciplinary research program that addresses the challenge through two primary strategies: the development of innovative technological advancements in treatment delivery and a deeper understanding of the underlying biological mechanisms.
A selection of our projects:
Particle therapy providers are advancing technologies like proton Arc therapy, delivering continuous radiation doses while rotating around the patient, and proton FLASH therapy, which administers high doses at ultra-high rates. Additionally, carbon ion therapy targets hypoxic tumors, offering advantages over traditional methods. The D-CAF project aims to facilitate market integration of these modalities by developing a next-generation dosimetry kit, including Monte Carlo codes to characterize ionization chambers under proton and carbon ion irradiations, enhancing accuracy and efficiency in cancer treatment.
A novel approach to predicting radiation susceptibility is being developed, utilizing DNA damage as a biomarker, with the collaboration of Dr. Costes’ laboratory at NASA Ames Research Center. Preclinical studies have shown a correlation between residual 53BP1 foci post-irradiation and cell death in murine blood, suggesting potential for predicting individual biological responses to radiation. Retrospective analysis revealed a higher level of spontaneous 53BP1 foci in prostate cancer patients associated with increased severity of radiation-induced side effects, and ongoing clinical trials aim to validate this marker’s utility.
Selected Publications:
Ionizing radiation responses appear incidental to desiccation responses in the bdelloid rotifer Adineta vaga.
Moris, V. C., Bruneau, L., Berthe, et al. BMC biology, 22(1), 11. (2024) DOI: 10.1186/s12915-023-01807-8
C. elegans: A potent model for high-throughput screening experiments investigating the FLASH effect.
Schoenauen, L., Stubbe, F. X., Van Gestel, et al. Clinical and translational radiation oncology, 100712 (2024) DOI: 10.1016/j.ctro.2023.100712
Radiation therapy-activated nanoparticle and immunotherapy: The next milestone in oncology?
Penninckx, S., Thariat, J., & Mirjolet, C. International Review of Cell and Molecular Biology, 378, 157-200 (2023). DOI: 10.1016/bs.ircmb.2023.03.005
Back to the roots, desiccation and radiation resistances are ancestral characters in bdelloid rotifers.
Hespeels, B., Fontaneto, D., Cornet, V., et al. BMC biology, 21(1), 72 (2023). DOI: 10.1186/s12915-023-01554-w
Advances in the Mechanistic Understanding of Iron Oxide Nanoparticles’ Radiosensitizing Properties
Ternad, I., Penninckx, S., Lecomte, V., et al. Nanomaterials, 13(1), 201. (2023). DOI: 10.3390/nano13010201
Radiation-activated nanoparticles: Which combination to optimize radiosensitization?
Penninckx, S., Martinive, P., & Mirjolet, C. Cancer/Radiothérapie, 27(6-7), 494-498. (2023). DOI: 10.1016/j.canrad.2023.07.002
Understanding the Radiobiological Mechanisms Induced by 177Lu-DOTATATE in Comparison to External Beam Radiation Therapy
Delbart, W., Karabet, J., Marin, G., et al. Int J of molecular sciences, 23(20), 12369. (2022). DOI: 10.3390/ijms232012369
Mouse genomic associations with in vitro sensitivity to simulated space radiation.
Cekanaviciute, E., Tran, D., Nguyen, H., et al. Life Sciences in Space Research, 36, 47-58. (2022). DOI: 10.1016/j.lssr.2022.07.006
Quantification of radiation-induced DNA double strand break repair foci to evaluate and predict biological responses to ionizing radiation
Penninckx, S., Pariset, E., Cekanaviciute, E., et al. NAR cancer, 3(4), zcab046. (2021). DOI: 10.1093/narcan/zcab046
Metallic Nanoparticles: A Useful Prompt Gamma Emitter for Range Monitoring in Proton Therapy?
Penninckx, S., Hespeels, F., Smeets, J., et al. Radiation, 1(4), 305-316 (2021). DOI: 10.3390/radiation1040025
Considering cell proliferation to optimize detection of radiation-induced 53BP1 positive foci in 15 mouse strains ex vivo
Penninckx, S., Pariset, E., Acuna, A. U., et al. Radiation Research, 195(1), 47-59. (2021). DOI: 10.1667/RADE-20-00165.1
A selection of our projects:
- TheraNCT – Development of personalized neutron capture therapy using theranostic carriers:
- FLASH4Clinic – Unravelling the open questions in FLASH preclinical radiotherapy for an optimal clinical translation :
- D-CAF: Dosimetry for Carbon, ARC and FLASH therapies
Particle therapy providers are advancing technologies like proton Arc therapy, delivering continuous radiation doses while rotating around the patient, and proton FLASH therapy, which administers high doses at ultra-high rates. Additionally, carbon ion therapy targets hypoxic tumors, offering advantages over traditional methods. The D-CAF project aims to facilitate market integration of these modalities by developing a next-generation dosimetry kit, including Monte Carlo codes to characterize ionization chambers under proton and carbon ion irradiations, enhancing accuracy and efficiency in cancer treatment.
- PRISME: Predicting Radiation Sensitivity via Marker Evaluation
A novel approach to predicting radiation susceptibility is being developed, utilizing DNA damage as a biomarker, with the collaboration of Dr. Costes’ laboratory at NASA Ames Research Center. Preclinical studies have shown a correlation between residual 53BP1 foci post-irradiation and cell death in murine blood, suggesting potential for predicting individual biological responses to radiation. Retrospective analysis revealed a higher level of spontaneous 53BP1 foci in prostate cancer patients associated with increased severity of radiation-induced side effects, and ongoing clinical trials aim to validate this marker’s utility.
Selected Publications:
Ionizing radiation responses appear incidental to desiccation responses in the bdelloid rotifer Adineta vaga.
Moris, V. C., Bruneau, L., Berthe, et al. BMC biology, 22(1), 11. (2024) DOI: 10.1186/s12915-023-01807-8
C. elegans: A potent model for high-throughput screening experiments investigating the FLASH effect.
Schoenauen, L., Stubbe, F. X., Van Gestel, et al. Clinical and translational radiation oncology, 100712 (2024) DOI: 10.1016/j.ctro.2023.100712
Radiation therapy-activated nanoparticle and immunotherapy: The next milestone in oncology?
Penninckx, S., Thariat, J., & Mirjolet, C. International Review of Cell and Molecular Biology, 378, 157-200 (2023). DOI: 10.1016/bs.ircmb.2023.03.005
Back to the roots, desiccation and radiation resistances are ancestral characters in bdelloid rotifers.
Hespeels, B., Fontaneto, D., Cornet, V., et al. BMC biology, 21(1), 72 (2023). DOI: 10.1186/s12915-023-01554-w
Advances in the Mechanistic Understanding of Iron Oxide Nanoparticles’ Radiosensitizing Properties
Ternad, I., Penninckx, S., Lecomte, V., et al. Nanomaterials, 13(1), 201. (2023). DOI: 10.3390/nano13010201
Radiation-activated nanoparticles: Which combination to optimize radiosensitization?
Penninckx, S., Martinive, P., & Mirjolet, C. Cancer/Radiothérapie, 27(6-7), 494-498. (2023). DOI: 10.1016/j.canrad.2023.07.002
Understanding the Radiobiological Mechanisms Induced by 177Lu-DOTATATE in Comparison to External Beam Radiation Therapy
Delbart, W., Karabet, J., Marin, G., et al. Int J of molecular sciences, 23(20), 12369. (2022). DOI: 10.3390/ijms232012369
Mouse genomic associations with in vitro sensitivity to simulated space radiation.
Cekanaviciute, E., Tran, D., Nguyen, H., et al. Life Sciences in Space Research, 36, 47-58. (2022). DOI: 10.1016/j.lssr.2022.07.006
Quantification of radiation-induced DNA double strand break repair foci to evaluate and predict biological responses to ionizing radiation
Penninckx, S., Pariset, E., Cekanaviciute, E., et al. NAR cancer, 3(4), zcab046. (2021). DOI: 10.1093/narcan/zcab046
Metallic Nanoparticles: A Useful Prompt Gamma Emitter for Range Monitoring in Proton Therapy?
Penninckx, S., Hespeels, F., Smeets, J., et al. Radiation, 1(4), 305-316 (2021). DOI: 10.3390/radiation1040025
Considering cell proliferation to optimize detection of radiation-induced 53BP1 positive foci in 15 mouse strains ex vivo
Penninckx, S., Pariset, E., Acuna, A. U., et al. Radiation Research, 195(1), 47-59. (2021). DOI: 10.1667/RADE-20-00165.1