Project description
Characterising multilevel mechanisms of targeted radionuclide therapy
Radiotherapy of tumours has seen tremendous advances in the last several decades relative to the potentially cancer-causing and non-selective radiation of earlier years. Targeted radionuclide therapy (TRT), like chemotherapy, is a systemic treatment. It relies on a cancer cell-targeting molecule labelled with a radionuclide to deliver toxic radiation directly to the tumour site. While TRTs are very promising, optimising treatments requires better understanding of their specific radiobiological effects. The EU-funded RADIOBIO project will yield critical information on subcellular and intratumoural radiopharmaceutical uptake kinetics, DNA damage response kinetics and dose response simulations while delivering a novel imaging technique to image real-time cellular processes of anti-cancer therapies in a living organism.
Objective
Background and unmet need
Targeted radionuclide therapies (TRTs) are a promising modality to treat patients with metastasized cancer. TRTs function via systemic administration of radiolabelled molecules (α- and β-particle emitters) designed to target tumour cells. However, the radiobiological 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. Since most patients with advanced cancer cannot be cured at the moment, it is therefore my ultimate goal to improve TRT.
Aim
My ERC project aims to identify and quantitate specific radiobiological mechanisms of TRT-radiation effects in vitro and in vivo.
Objectives
This unique multidisciplinary project will yield critical information on subcellular and intra-tumoural radiopharmaceutical uptake kinetics, DNA damage response kinetics and dose response simulations, and will profoundly increase our knowledge on TRT to push the field forward. I will determine cellular dosimetric parameters for α-TRT and β-TRT, determine effects of subcellular and intra-tumoural localizations of TRT on DNA damage induction and survival, image in vivo TRT efficacy and define effects of treatment heterogeneity to ultimately perform realistic dosimetric simulations in 2D and 3D cancer models. Besides using previously developed techniques, we will develop an innovative new imaging setup for high resolution imaging of TRT by intravital confocal microscopy to image real-time cellular processes of anti-cancer therapies in a living organism.
Expected Outcomes
Outcome of my project will not only increase our fundamental knowledge on TRT and yield a novel imaging modality, but additionally has high potential to contribute to improved treatment strategies and ultimately patient outcomes.
Fields of science
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Topic(s)
Funding Scheme
HORIZON-AG - HORIZON Action Grant Budget-BasedHost institution
3015 GD Rotterdam
Netherlands