Simona Mattiussi | OncoProTools | University of Antwerp

Supervisor: Prof. Dr. Matthias M. Herth
Institution: University of Copenhagen
Defended: 13 March 2026

Abstract: Cancer remains a major global health challenge, with rising incidence and mortality rates worldwide. Despite advances in oncology, early detection, accurate treatment monitoring, and effective therapy for solid tumors remain limited. Theranostics, combining molecular imaging with targeted radionuclide therapy, has emerged as a precision medicine approach to improve patient selection and reduce systemic toxicity. Tumor heterogeneity and the supportive tumor microenvironment, particularly cancer-associated fibroblasts, contribute significantly to therapeutic resistance. Fibroblast activation protein (FAP), highly expressed in these stromal cells and minimally in normal tissues, represents a promising universal target. While FAP inhibitors have shown strong performance in PET imaging, their therapeutic translation is limited by suboptimal tumor retention and pharmacokinetics. Meanwhile, immunotherapies such as CAR T-cell therapy face challenges in solid tumors, prompting the development of controllable platforms like Universal CAR T cells and combination strategies with radionuclide therapy.

This Ph.D. thesis focuses on developing and optimizing novel small-molecule FAP-targeting compounds for theranostic applications. The work improves tumor uptake and retention, explores pretargeting strategies integrating nuclear and near-infrared imaging, and develops a FAP-based module for combined radionuclide delivery and Universal CAR T-cell therapy. Overall, the project advances the field of FAP-targeted theranostics.