Record #343343 - GSI Repository

POLYTROP

Development of Novel Multimodal Dextran-Based Theranostic Tracers: Targeting Fibroblast Activation Protein as Proof of Concept

Grant period	2023-06-01 - 2025-05-31
Funding body	European Union
Call number	HORIZON-WIDERA-2022-TALENTS-04
Grant number	101130787
Identifier	G:(EU-Grant)101130787

Note: According to WHO, cancer is a leading cause of death worldwide, accounting for nearly 20 million new cases and 10 million deaths in 2020. This project addresses the development of a novel compound targeting the fibroblast activation protein, overexpressed in more than 90% of human epithelial cancers. It combines up to four imaging techniques (single-photon emission computed tomography, positron emission tomography, magnetic resonance, and optical imaging) and two therapeutic approaches (radionuclide therapy and boron neutron capture therapy (BNCT)). The novel compound is based on a dextran scaffold, which acts as a backbone for attachment of i) a FAP-inhibitor based on a quinoline structure, ii) a macrocycle chelator for complexation with Gadolinium, Technetium-99m, Rhenium-188, Gallium-68, and Lutetium-177 for imagining or radionuclide therapy, iii) carborane for BNCT and iv) fluorescent dye for optical imaging. The aim is to achieve a tailor-made combination of unique and versatile properties by adapting the multifunctional structure of the ligand compound throughout different imaging and therapeutic procedures using a simple and robust labeling protocol, exploiting the outstanding properties of each moiety and conferring our compound with precisely designed functionalities. The implementation and delivery of high-impact outcomes will be achieved following a well-defined route. The long-term objective of this project is to determine whether vial kits for imaging and therapy can be developed. The novel ligand will be synthesized following well-established methodologies and fully characterized by elemental analysis, IR, and NMR. Then, the radiolabeling procedures of the ligand with the radionuclides will be optimized, and a kit formulation will be developed. At the same time, the project will determine the inhibitory activities of the radiolabeled compounds and their applicability for in vivo imaging and radionuclide therapy in FAP-positive tumor-bearing mice.

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Record created 2023-08-27, last modified 2023-08-27

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