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Next-Generation FAP Tracers: Single-Domain Antibody–FAPI Conjugates for Cancer Theranostics

Objective

This proposal aims to create next-generation molecular imaging probes for cancer by targeting the fibroblast activation protein (FAP), a prominent biomarker of cancer-associated fibroblasts. FAP small-molecule inhibitors (FAPIs) have recently shown great promise for PET imaging, enabling sensitive visualization of tumors across multiple cancer types. However, despite their clinical impact, current FAPIs suffer from rapid systemic clearance and limited tumor retention, restricting their diagnostic sensitivity and therapeutic applicability. To address these shortcomings, this project introduces an innovative multivalent strategy that combines the potency of FAPIs with the specificity of single-domain antibodies (sdAbs). The proposal is structured around four main objectives: (1) systematic identification and characterization of sdAbs with strong affinity, high residence time, stability, and favorable biophysical properties; (2) chemical synthesis and optimization of sdAb–FAPI conjugates with tailored linkers to maximize stability and functionality; (3) structural and mechanistic validation of binding interactions using cryo-electron microscopy (cryo-EM), providing molecular-level insights for rational probe design; and (4) radiolabeling of the most promising conjugates and preclinical validation in PET/SPECT imaging to benchmark their performance against reference FAP tracers. By combining approaches from , chemical biology, structural biology, enzymology and radiopharmacy, the proposal will deliver innovative FAP-targeted probes with enhanced tumor retention, improved imaging quality, and expanded theranostic potential. These outcomes will not only advance cancer diagnostics but may also open new opportunities for treating diseases characterized by FAP expression.

Fields of science (EuroSciVoc)

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Keywords

Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)

Programme(s)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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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) HORIZON-MSCA-2025-PF

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Coordinator

UNIVERSITEIT ANTWERPEN
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.

€ 200 400,00
Address
PRINSSTRAAT 13
2000 Antwerpen
Belgium

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Region
Vlaams Gewest Prov. Antwerpen Arr. Antwerpen
Activity type
Higher or Secondary Education Establishments
Links
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.

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