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C2RTheranostics

Financiado

Exploring a click-to-release approach to uncage FAP-theranostics, based on TCO-r...

Exploring a click-to-release approach to uncage FAP-theranostics, based on TCO-radiotracers Radioligand therapy has recently received renewed attention as promising treatment option to improve cancer patient outcome. Compared to conventional cancer treatments, this strategy involves a more specific targeting of therapeut... ver más

30/06/2026

UANTWERPEN

176K€

Presupuesto del proyecto: 176K€

Líder del proyecto

UNIVERSITEIT ANTWERPEN No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2024-03-13

HORIZON-MSCA-2023-PF-01-01: MSCA Postdoctoral Fellowships 2023 ExpectedOutcome:Project results are expected to contribute to the following outcomes:

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1 Participantes

UANTWERPEN

175.92K€ | Lider

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Duración del proyecto: 27 meses Fecha Inicio: 2024-03-13
Fecha Fin: 2026-06-30

Líder del proyecto

UNIVERSITEIT ANTWERPEN No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 176K€

Descripción del proyecto Radioligand therapy has recently received renewed attention as promising treatment option to improve cancer patient outcome. Compared to conventional cancer treatments, this strategy involves a more specific targeting of therapeutic radionuclides to the tumor, which aims to increase treatment efficacy. Despite recent progress, currently available treatments show insufficient tumor killing and normal tissue toxicity, and we hypothesize that a pretargeted click-to-release (C2R) strategy can bridge this gap. Within this strategy, we propose to explore Fibroblast Activation Protein (FAP) inhibitors as tumor targeting vectors, to deliver a therapeutic radionuclide fragment intracellularly using cell permeable, cleavable transcyclooctene (dcTCO) constructs and compare it with conventional dTCOs. To reinsure intracelular release, after C2R, we designed new structures containing an RGD peptide (with integrin αvβ3 binding specificity). Our molecular constructs also aim to prevent FAP efflux, by using a guanidinium and nicotinoyl residualizing groups. This project will evaluate the reactivity, in vitro stability, logD and radiochemical yield of the new molecules, and the C2R efficiency of the dcTCOs. A FAP inhibitor (dimer) will be weaponized with a tetrazine handle to be the targeting vector and biorthogonal pair of these new constructs, and it's affinity and selectivity will be evaluated in vitro, against other proteases. The dcTCOs and dTCOs with better reaction kinetics and C2R efficiency (dcTCOs) will be selected for the development of 18F- and 125I-radiolabeled probes. The celular uptake and internalization will be evaluated on tumor cells (FAP positive cells, integrin αvβ3 positive cells, both FAP and αvβ3 positive). This project is a innovative strategy to improve the radiation dose delivered to the tumor and improving treatment outcome, while reducing radiotoxicity and achieving better treatment tolerability.

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