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Deciphering the radiobiology of targeted radionuclide therapy: from subcellular to intra-tumoural analyses

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.

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2021-STG

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Host institution

ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 750 000,00
Address
DR MOLEWATERPLEIN 40
3015 GD Rotterdam
Netherlands

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Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 750 000,00

Beneficiaries (1)

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