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About Dosimetry Core Unit (DCU)
The goal of the Dosimetry Core Unit (DCU) is to support effective and safe radionuclide therapy for cancer patients. To this aim, we perform translational research, covering the whole range from bench to bedside to community.
read moreAbout Dosimetry Core Unit (DCU)
The goal of the Dosimetry Core Unit is to support effective and safe radionuclide therapy for cancer patients. To this aim, we perform translational research, covering the whole range from bench to bedside to community. Knowledge and expertise is used within the DCU to work on three important sub-goals:
- Accurate absorbed dose calculations for safe and effective radionuclide therapy for personalized treatment in patients.
- Development of new suitable tracers for radionuclide therapy, photodynamic therapy and pre-clinical dosimetry.
- Obtaining fundamental knowledge about dose-effect relationships.
Organization
The Dosimetry Core Unit is part of the Department of Medical Imaging at the Radboud university medical center, specifically of the NucMed Research group. We join forces with other departments at Radboudumc, such as Radiation Oncology, and other institutions such as Erasmus MC.
read moreOrganization
The Dosimetry Core Unit is part of the Department of Medical Imaging at the Radboud university medical center, specifically of the NucMed Research group.
We join forces with colleagues at other departments at Radboudumc, such as Radiation Oncology, and with colleagues from other institutions, such as Erasmus MC. These colleagues are also part of our Dosimetry Core Unit, so we can make sure we have as much dosimetry knowledge available as possible. We are always open to new collaborations, so please contact us if you have any questions.
Structure
The Dosimetry Core Unit is part of the Medical Physics group. This team coordinates (inter)national collaboration and networking, ensures the availability of in-depth dosimetry knowledge, can provide internal and external dosimetry training and coordinates contract research related to dosimetry. The organization of the Dosimetry Core Unit is structured around 3 pillars:
- Systemic therapy
- Radioembolization
- Photodynamic therapy
For all pillars, we try to cover the whole translational range of research, from cell-based experiments, to pre-clinical research and clinical studies. Each combination of pillar and type of research is coordinated by a dedicated physician/researcher, as can be seen in the structured overview of the Dosimetry Core Unit. These physicians/researchers have in-depth knowledge on these areas and can coordinate with the Dosimetry Core Unit on specific dosimetry questions.
Published papers
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Gabiña PM, Gleisner KS, Cremonesi M, Stokke C, Flux G, Cicone F, Konijnenberg M, Aldridge M, Sandstrom M, Chiesa C, Paphiti M, Hippeläinen E, Uribe C, Solny P, Gnesin S, Bernhardt P, Chouin N, Costa PF, Glatting G, Verburg F, Gear J. Results from an EANM survey on time estimates and personnel responsible for main tasks in molecular radiotherapy dosimetry. Eur J Nucl Med Mol Imaging. 2023 Jul;50(9):2595-2604.
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Maarten de Bakker, Noa Dominicus, Antoi Meeuwis, Marcel Janssen, Mark W Konijnenberg, James Nagarajah, Steffie M B Peters. Urinary excretion kinetics of [177Lu]Lu-PSMA-617. Eur J Nucl Med Mol Imaging. 2023 Jul 8. doi: 10.1007/s00259-023-06328-8. Online ahead of print.
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Handula M, Beekman S, Konijnenberg M, Stuurman D, de Ridder C, Bruchertseifer F, Morgenstern A, Denkova A, de Blois E, Seimbille Y. First preclinical evaluation of [225Ac]Ac-DOTA-JR11 and comparison with [177Lu]Lu-DOTA-JR11, alpha versus beta radionuclide therapy of NETs. EJNMMI Radiopharm Chem. 2023 Jun 30;8(1):13.
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Snoeijink TJ, Vlogman TG, Roosen J, Groot Jebbink E, Jain K, Nijsen JFW. Transarterial radioembolization: a systematic review on gaining control over the parameters that influence microsphere distribution. Drug Deliv. 2023 Dec;30(1):2226366.
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Kuo PH, Yoo DC, Avery R, Seltzer M, Calais J, Nagarajah J, Weber WA, Fendler WP, Hofman MS, Krause BJ, Brackman M, Kpamegan E, Ghebremariam S, Benson T, Catafau AM, Kendi AT. A VISION Substudy of Reader Agreement on 68Ga-PSMA-11 PET/CT Scan Interpretation to Determine Patient Eligibility for 177Lu-PSMA-617 Radioligand Therapy. J Nucl Med. 2023 May 25:265077. Online ahead of print.
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Gabiña PM, Gleisner KS, Cremonesi M, Stokke C, Flux G, Cicone F, Konijnenberg M, Aldridge M, Sandstrom M, Chiesa C, Paphiti M, Hippeläinen E, Uribe C, Solny P, Gnesin S, Bernhardt P, Chouin N, Costa PF, Glatting G, Verburg F, Gear J. Results from an EANM survey on time estimates and personnel responsible for main tasks in molecular radiotherapy dosimetry. Eur J Nucl Med Mol Imaging. 2023 May 2. Online ahead of print.
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Quist SW, Paulissen JHJ, Wyndaele DNJ, Nagarajah J, Freriks RD. Costs of radium-223 and the pharmacy preparation 177Lu-PSMA-I&T for metastatic castration-resistant prostate cancer in Dutch hospitals. J Med Econ. 2023 Jan-Dec;26(1):366-375.
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Siebinga H, Privé BM, Peters SMB, Nagarajah J, Dorlo TPC, Huitema ADR, de Wit-van der Veen BJ, Hendrikx JJMA. Population pharmacokinetic dosimetry model using imaging data to assess variability in pharmacokinetics of 177 Lu-PSMA-617 in prostate cancer patients. CPT Pharmacometrics Syst Pharmacol. 2023 Feb 9.
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Pouget JP, Konijnenberg M, Eberlein U, Glatting G, Gabina PM, Herrmann K, Holm S, Strigari L, van Leeuwen FWB, Lassmann M. An EANM position paper on advancing radiobiology for shaping the future of nuclear medicine. EANM Radiobiology Working Group. Eur J Nucl Med Mol Imaging. 2023 Jan;50(2):242-246.
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Ruigrok EAM, Verhoeven M, Konijnenberg MW, de Blois E, de Ridder CMA, Stuurman DC, Bertarione L, Rolfo K, de Jong M, Dalm SU. Safety of [177Lu]Lu-NeoB treatment: a preclinical study characterizing absorbed dose and acute, early, and late organ toxicity. Eur J Nucl Med Mol Imaging. 2022 Aug 11. Online ahead of print
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Joey Roosen, Lovisa E L Westlund Gotby, Mark J Arntz, Jurgen J Fütterer, Marcel J R Janssen, Mark W Konijnenberg, Meike W M van Wijk, Christiaan G Overduin, J Frank W Nijsen. Intraprocedural MRI-based dosimetry during transarterial radioembolization of liver tumours with holmium-166 microspheres (EMERITUS-1): a phase I trial towards adaptive, image-controlled treatment delivery. Eur J Nucl Med Mol Imaging. 2022 Jul 13.
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Bastiaan M Privé, Steffie M B Peters, Maike J M Uijen, Marcel J R Janssen, Willemijn A M van Gemert, Michael C Kreissl, Samer Ezzidin, Mark W Konijnenberg, James Nagarajah. Thoughts on "Tumor Sink Effect in 68 Ga-PSMA-11 PET: Myth or Reality?" J Nucl Med. 2022 Jul;63(7):1124-1125. Epub 2022 Jan 13.
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Lorain Geenen, Julie Nonnekens, Mark Konijnenberg, Sarah Baatout, Marion De Jong, An Aerts. Overcoming nephrotoxicity in peptide receptor radionuclide therapy using [ 177 Lu]Lu-DOTA-TATE for the treatment of neuroendocrine tumours. Nucl Med Biol. 2021 Nov-Dec; 102-103:1-11.
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Katarina Sjögreen Gleisner, Nicolas Chouin, Pablo Minguez Gabina, Francesco Cicone, Silvano Gnesin, Caroline Stokke, Mark Konijnenberg, Marta Cremonesi, Frederik A Verburg, Peter Bernhardt, Uta Eberlein, Jonathan Gear. EANM dosimetry committee recommendations for dosimetry of 177Lu-labelled somatostatin-receptor- and PSMA-targeting ligands. Eur J Nucl Med Mol Imaging. 2022 May;49(6):1778-1809.
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Giulia Tamborino, Julie Nonnekens, Lara Struelens, Marijke De Saint-Hubert, Frederik A Verburg, Mark W Konijnenberg. Therapeutic efficacy of heterogeneously distributed radiolabelled peptides: Influence of radionuclide choice. Phys Med. 2022 Apr; 96:90-100.
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Eline A.M. Ruigrok, Giulia Tamborino, Erik de Blois, Stefan J. Roobol, Nicole Verkaik, Marijke De Saint-Hubert, Mark W. Konijnenberg, Wytske M. van Weerden, Marion de Jong, Julie Nonnekens. In vitro dose effect relationships of actinium-225- and lutetium-177-labeled PSMA-I&T. Eur J Nucl Med Mol Imaging (2022). https://doi.org/10.1007/s00259-022-05821-w.
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Banda A, Privé BM, Allach Y, Uijen MJM, Peters SMB, Loeff CC, Gotthardt M, Muselaers CHJ, Witjes JA, van Oort IM, Sedelaar JPM, Westdorp H, Mehra N, Khreish F, Ezziddin S, Sabet A, Kreissl MC, Winkens T, Seifert P, Janssen MJR, van Gemert WAM, Nagarajah J. PSMA-RLT in Patients with Metastatic Hormone-Sensitive Prostate Cancer: A Retrospective Study. Cancers (Basel). 2022 Dec 31;15(1):297.
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Uijen MJM, Privé BM, van Herpen CML, Westdorp H, van Gemert WA, de Bakker M, Gotthardt M, Konijnenberg MW, Peters SMB, Nagarajah J. Kidney absorbed radiation doses for [177Lu]Lu-PSMA-617 and [177Lu]Lu-PSMA-I&T determined by 3D clinical dosimetry. Nucl Med Commun. 2023 Jan 4. Online ahead of print.
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Ruigrok EAM, Verhoeven M, Konijnenberg MW, de Blois E, de Ridder CMA, Stuurman DC, Bertarione L, Rolfo K, de Jong M, Dalm SU. Safety of [177Lu]Lu-NeoB treatment: a preclinical study characterizing absorbed dose and acute, early, and late organ toxicity. Eur J Nucl Med Mol Imaging. 2022 Nov;49(13):4440-4451.
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Roosen J, van Wijk MWM, Gotby LELW, Arntz MJ, Janssen MJR, Lobeek D, van de Maat GH, Overduin CG, Nijsen JFW. Improving MRI-based dosimetry for holmium-166 transarterial radioembolization using a non-rigid image registration for voxelwise calculation. Med Phys. 2022 Oct 6.
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Lassmann M, Eberlein U, Gear J, Konijnenberg M, Kunikowska J.. Dosimetry for radiopharmaceutical therapy: the European perspective. J Nucl Med. 2021 Dec; 62(Suppl3):73S-79S.
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Roosen J, Arntz MJ, Janssen MJR, de Jong SF, Fütterer JJ, Overduin CG, Nijsen JFW. Development of an MRI-Guided Approach to Selective Internal Radiation Therapy Using Holmium-166 Microspheres. Cancers (Basel). 2021 Oct 30;13(21):5462.
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Chiesa C, Sjogreen-Gleisner K, Walrand S, Strigari L, Flux G, Gear J, Stokke C, Gabina PM, Bernhardt P, Konijnenberg M. EANM dosimetry committee series on standard operational procedures: a unified methodology for 99mTc-MAA pre- and 90Y peri-therapy dosimetry in liver radioembolization with 90Y microspheres. EJNMMI Phys. 2021 Nov 12;8(1):77.
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Roosen J, Klaassen NJM, Westlund Gotby LEL, Overduin CG, Verheij M, Konijnenberg MW, Nijsen JFW. To 1000 Gy and back again: a systematic review on dose-response evaluation in selective internal radiation therapy for primary and secondary liver cancer. Eur J Nucl Med Mol Imaging. 2021 Nov;48(12):3776-3790.
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de Vries M, Klaassen NJM, Morsink NC, van Nimwegen SA, Nijsen JFW, van den Dobbelsteen JJ. Dedicated holmium microsphere administration device for MRI-guided interstitial brain microbrachytherapy. Med Eng Phys. 2021 Oct;96:13-21.
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Peters, SMB et al. [68Ga]Ga-PSMA-11 PET imaging as a predictor for absorbed doses in organs at risk and small lesions in [177Lu]Lu-PSMA-617 treatment. Eur J Nucl Med Mol Imaging. 2021 Oct 8. Online ahead of print
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Taborino, G et al. Modeling early radiation DNA damage occurring during [ 177 Lu]Lu-DOTA-[Tyr 3]octreotate radionuclide therapy. J Nucl Med.
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Peters, SMB et al. Intra-therapeutic dosimetry of [(177)Lu]Lu-PSMA-617 in low-volume hormone-sensitive metastatic prostate cancer patients and correlation with treatment outcome. Eur J Nucl Med Mol Imaging.
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Geenen et al. Overcoming nephrotoxicity in peptide receptor radionuclide therapy using [177Lu]Lu-DOTA-TATE for the treatment of neuroendocrine tumours. Nucl Med Biol.
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Aerts, A et al. EANM position paper on the role of radiobiology in nuclear medicine. Eur J Nucl Med Mol Imaging.
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Privé, BM et al. Lutetium-177-PSMA-617 in Low-Volume Hormone-Sensitive Metastatic Prostate Cancer: A Prospective Pilot Study. Clin Cancer Res.
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Roosen, J et al. To 1000 Gy and back again: a systematic review on dose-response evaluation in selective internal radiation therapy for primary and secondary liver cancer. Eur J Nucl Med Mol Imaging.
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Dotinga, M et al. Managing radioiodine refractory thyroid cancer: the role of dosimetry and redifferentiation on subsequent I-131 therapy. Q J Nucl Med Mol Imaging.
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Tamborino, G et al. Dosimetric evaluation of receptor-heterogeneity on the therapeutic efficacy of peptide receptor radionuclide therapy: correlation with DNA damage induction and in vivo survival. J Nucl Med.
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Konijnenberg et al. EANM position paper on article 56 of the Council Directive 2013/59/Euratom (basic safety standards) for nuclear medicine therapy. Eur J Nucl Med Mol Imaging.
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Feijtel, D et al. Intra-tumoral somatostatin receptor 2 heterogeneity confers differential radionuclide therapy response in preclinical neuroendocrine tumor models. Theranostics.
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Dijkstra, BM et al. Evaluation of Ac-Lys0(IRDye800CW)Tyr3-octreotate as a novel tracer for SSTR2-targeted molecular fluorescence guided surgery in meningioma. J Neuro-oncol. 2021 Mar 26.
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- Huizing, DMV et al. A head-to-head comparison between two commercial software packages for hybrid dosimetry after peptide receptor radionuclide therapy. EJNMMI Phys.
- Peters, SMB et al. Variability in lutetium-177 SPECT quantification between different state-of-the-art SPECT/CT systems. EJNMMI Phys.
- Boss, M et al. PET-Based Human Dosimetry of (68)Ga-NODAGA-Exendin-4, a Tracer for beta-Cell Imaging. J Nucl Med.
- Ruigrok EAM, van Vliet N, Dalm SU, de Blois E, van Gent DC, Haeck JC, de Ridder C, Stuurman D, Konijnenberg MW, van Weerden WM, de Jong M, Nonnekens J. Extensive preclinical evaluation of lutetium-177 labeled PSMA-specific tracers for prostate cancer radionuclide therapy. Eur J Nucl Med Mol Imaging. 2020 Oct 23.
- Reuvers T, Kanaar R, Nonnekens J. DNA damaging inducing anticancer therapies: from global to precision damage. Cancers (Basel). 2020 Jul 28;12(8):2098.
- Tamborino G, De Saint-Hubert M, Struelens L, Seoane DC, Ruigrok EAM, Aerts A, van Cappellen WA, de Jong M, Konijnenberg MW, Nonnekens J. DNA damaging inducing anticancer therapies: from global to precision damage. EJNMMI Phys. 2020 Feb 10;7(1):8.
- Peters, SMB et al. Towards standardization of absolute SPECT/CT quantification: a multi-center and multi-vendor phantom study. EJNMMI Phys.
- O'Neill, E et al. Imaging DNA Damage Repair In Vivo After 177Lu-DOTATATE Therapy. J Nucl Med.
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- Kratochwil, C et al. EANM procedure guidelines for radionuclide therapy with 177Lu-labelled PSMA-ligands (177Lu-PSMA-RLT). Eur J Nucl Med Mol Imaging.
- Ruigrok EAM, van Weerden WM, Nonnekens J#, de Jong M. The Future of PSMA-Targeted Radionuclide Therapy: An Overview of Recent Preclinical Research. Pharmaceutics. 2019 Oct 29;11(11):560.
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- Gear, JI et al. EANM practical guidance on uncertainty analysis for molecular radiotherapy absorbed dose calculations. Eur J Nucl Med Mol Imaging.
- Ruhlmann, M et al. Pretherapeutic 124I dosimetry reliably predicts intratherapeutic blood kinetics of 131I in patients with differentiated thyroid carcinoma receiving high therapeutic activities. Nucl Med Commun.
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- Stokke C, et al. Dosimetry-based treatment planning for molecular radiotherapy: a summary of the 2017 report from the Internal Dosimetry Task Force. EJNMMI Phys.
- Van der Kroon et al. Whole organ and islet of Langerhans dosimetry for calculation of absorbed doses resulting from imaging with radiolabeled exendin. Sci Rep.
Pillars
Central Dosimetry team
The Central Dosimetry team consists of members of the Medical Physics team and senior researchers. The Central Dosimetry team ensures the availability of in-depth dosimetry knowledge and coordinates (inter)national collaboration and networking.
read moreSystemic therapy
For dosimetry, the focus of this pilar is currently on PSMA ligands and antibodies, DOTATATE and CAIX. We perform cell and pre-clinical research to better understand the mode of action of both the diagnostic and therapeutic radiotracers.
read moreSystemic therapy
For dosimetry, the focus of this pilar is currently on PSMA ligands and antibodies, DOTATATE and CAIX. For example, we work on clinical dosimetry for therapy with 177Lu-PSMA, and pre-therapeutic dosimetry using PET imaging and PSMA labeled with isotopes such as 68Ga, 18F, but also longer lived isotopes such as 89Zr. We perform cell and pre-clinical research to better understand the mode of action of both the diagnostic and therapeutic radiotracers. For this, we also focus on application of alpha-emitters, as well as on radiobiological effects and immune response. This knowledge can then be used for translation into clinical application.
Radioembolization
This pilar focuses on dosimetry in radioembolization procedures. The main interest is the use of 166Ho-microspheres, for which MRI can also be used for dosimetry.
read moreRadioembolization
This pilar focuses on dosimetry in radioembolization procedures. The main importance is the use of optimized imaging procedures based on high-resolution MRI and CT imaging. For this purpose, 166Ho microspheres are used that are visible with both MRI and CT and can therefore achieve accurate dosimetry. But the application of 90y microspheres is also being investigated in relation to dose-response. For dosimetry in radioembolization procedures, identification of local inhomogeneities in the absorbed dose is important, as this information can be used to optimize the treatment plan and define the microsphere administration sites. We aim to enable real-time dosimetry during imaging-guided interventions to optimize the patient-specific treatment.
Photodynamic therapy
Dosimetry in photodynamic therapy (PDT) is still in its infancy, but very relevant to better understand the photobiological and immunological responses of this type of treatment. This pilar will currently mainly focus on pre-clinical models, for later translation into clinical research.
Our research
Clinical research
Our clinical dosimetry research can be divided in dosimetry used in systemic therapies and local therapies (radio-embolization). We currently don’t perform clinical dosimetry research related to photodynamic therapy.
Preclinical research
Our preclinical research focuses both on radionuclide therapy and photodynamic therapy. In both cases, we work on the development of new tracers for radionuclide/photodynamic therapy, mainly for applications that currently lack the availability of suitable therapeutic tracers.
read morePreclinical research
Our preclinical research focuses both on radionuclide therapy and photodynamic therapy. In both cases, we work on the development of new tracers for radionuclide/photodynamic therapy, mainly for applications that currently lack the availability of suitable therapeutic tracers. Using dosimetry, we can determine if tracer accumulation in tumors is sufficient to slow down tumor growth, while uptake in healthy organs is minimal. Furthermore, we focus on the development of PET-tracers that can be used for pre-therapeutic dosimetry, for which the predictive value is evaluated in preclinical mouse-models. In everything we do, the clinical need is our leading factor for our translational research and focus. Besides development of new tracers, we also work on microdosimetry and identifying radiobiological and immunological responses, since this is essential to understand dose-effect relationships.
Cell research
Our cell-dosimetry research focuses on identifying radionuclide inhomogeneities on subcellular level using fluorescent markers, and measuring cellular therapy responses such as DNA damage response.
read moreCell research
Our cell-dosimetry research focuses on identifying radionuclide inhomogeneities on subcellular level using fluorescent markers, and measuring cellular therapy responses such as DNA damage response. This detailed knowledge is generated using histology and live-cell microscopy, and will be integrated into dosimetric simulation models to evaluate new radionuclide therapies. This way, we can improve dose predictions which can be translated to mouse and man.
Dosimetry Core Unit members
