Our areas of research
Cellular effects of radionuclide in tumor cells
During targeted radionuclide therapy, radiolabeled compounds are targeted to the cancer cells via specific tumor binding (e.g. via receptors). Once bound to the tumor cells, the radionuclides will induce DNA damage leading to cancer cell death.
In order to gain insight in the underlying radiobiological principle of this therapy, we are studying human tumor cell line and slices cultured and treated in vitro with targeted radionuclide therapy. We are investigating the internalisation of TRT, the subsequent induced DNA damage, regulation of RNA expression, survival of tumor cells, etc
Current projects:
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Tumor radiobiology of NET TRT [Danny Feijtel, Pleun Engbers, Joke Zink, Giulia Tamborino, Tijmen de Wolf]
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Tumor cell radiobiology of PCa TRT [Eline Ruigrok, Mariangela Sabatella]
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Pathway activation analysis of NET TRT [Thom Reuvers, Mariangela Sabatella]
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Immune responses activated by TRT [Justine Perrin]
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Radiobiological assessment of blood of NET TRT patients [Nina Becx]
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Novel TRT options for pediatric neuro oncology [Nina Overdevest]
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Radiobiology and dosimetry of different radiation qualities
Various radionuclides are being used in clinical practice or expected to be implemented in the future, including Auger, alpha and beta emitter. Different radionuclides have different cellular effects based mostly on the type of decay, half-life and range. In order to predict which radionuclide is suitable for which indication, we are investigating the difference between these radiation qualities using in vitro biological experiments en in silico dose simulations
In addition, we are also focusing on development of detailed dosimetric modes. At the moment, there is no accurate method to determine the dose of TRT on various cellular targets and intratumoral heterogeneous regions. Therefore, it is essential to perform dosimetry to understand radiation dose-effects and integrate them into treatment planning systems for TRT.
Current projects:
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Live cell imaging of DNA repair dynamics by TRT [Pleun Engbers, Tijmen de Wolf, Justine Perrin]
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Radiobiological comparison of lutetium-177 and actinium-225 for PCa TRT [Eline Ruigrok, Mariangela Sabatella]
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Radiobiological comparison of lutetium-177 and terbium-161 [Joke Zink]
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Micro- and macrodosimetry of TRT [Giulia Tamborino]
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Automated image analysis of TRT fluorescent images [Tijmen de Wolf]
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Radiobiological comparison of holmium-166 and yttrium-90 for radioembolization [Justine Perrin]
Radiosensitization for improved radionuclide therapy outcome
Work by us and others has shown that TRT can be potentiated by combination with radiosensitizing compounds. Especially, various DDR inhibitors can function as radiosensitizers, and differentially impair DNA repair of TRT induced DNA damage and thereby vastly increase cell death, as we have shown in cells, tumor slices and xenografted tumors.
On key example is radiosensitization of TRT for neuroendocrine tumors using the PARP-1 inhibitor olaparib. Our preclinical work has led to the start of various clinical trials worldwide and we are now also performing our own clinical phase 1 trial (collaboration with Dr. Hans Hofland). In addition to PARP-1 inhibitors, we are using drug screens to identify other potential synergistic combinatory regimens.
Current projects:
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Radiosensitization to improve TRT outcome [Thom Reuvers, Danny Feijtel, Eline Ruigrok, Mariangela Sabatella]
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Clinical phase 1 trial of NET TRT in combination with PARP inhibitors [Nina Becx]
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For more details please contact:
Current vacacancies and internship
Vacancies
PhD student: unraveling the radiation biology of radioactive anticancer agents.
The project focuses on investigating cellular effects of radioactive anti-cancer agents as part of a Dutch NWO-funded consortium.
Job description
We are looking for a highly motivated PhD student to work on a project focusing on the radiation biology of targeted radionuclide therapy (TRT). This multidisciplinary project brings together expertise from the fields of nuclear medicine, molecular biology and cellular (radiation) biology.
TRT is a promising novel modality to treat patients with metastasized cancer. TRTs function via systemic administration of radiolabeled molecules designed to target tumor cells. However, the biological radiation effects of TRTs are poorly understood, and rational design of new modalities based on underlying cellular mechanisms is therefore not possible, resulting in suboptimal treatment strategies. In this preclinical research project, you will perform cellular experiments to identify and quantify specific radiobiological mechanisms of TRT-radiation effects.
In this project, you will be trained in using various laboratory techniques including cell culture, (fluorescent) microscopy, and different molecular biological techniques. Focus of this project will be on 2D cellular model systems and within the consortium, you will collaborate with colleagues from Radboud UMC who will work on 3D and in vivo radiobiology.
Internship
We welcome all students for internship positions.
If you are interested in doing an internship with us, please contact us via email : j.nonnekens@erasmusmc.nl
Current fundings
MSCA postdoctoral fellowship
Justine Perrin
2024-2026
Impact of BRCA2 deficiency on the DNA damage response and immunogenicity of prostate cancer after radioligand therapy.
NWO Perspectief consortium
Frank Nijsen, Julie Nonnekens, Sandra Heskamp, Antonia Denkova, consortium partners
2022-2027
Understanding the radiobiology of therapeutic medical radionuclides.
Research grant Cure Starts Now Foundation
Sophie Veldhuijzen van Zanten, Julie Nonnekens
2022-2026
Development and optimization of targeted radiopharmaceutical therapies for pediatric brain tumors; a world-first translational study.
ERC starting grant 2021
Julie Nonnekens
2022-2027
RADIOBIO: Deciphering the radiobiology of targeted radionuclide therapy: from subcellular to intra-tumoural analyses
Research collaboration with Quirem Medical, Terumo
Julie Nonnekens
2022-2024
Radiobiological effects of holmium-166 and yttrium-90
Research collaboration with POINT Biopharma
Julie Nonnekens
2022-2024
Radiobiology of alpha and beta-PSMA targeted radionuclide therapy
Oncode clinical proof of concept study
Roland Kanaar, Julie Nonnekens, Hans Hofland, Ferry Eskens, Wouter de Herder, Tessa Brabander, Astrid van der Veldt, Mark Konijnenberg, Stijn Koolen
2021-2024
Oncode clinical proof of concept study. “Improving Peptide Receptor Radionuclide Therapy with PARP inhibitors: the PRRT-PARPi study”.
Erasmus MC Fellowship 2019
Julie Nonnekens
2020-2024
RADIANT: cellular RADIAtion exposure effects of molecular radioNuclide Therapies
