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RESEARCH PRODUCT

Design of molecular imaging and theranostic agents for the detection and targeted therapy of cancers

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description

Despite significant advances in cancer detection and treatment, cancer is now the second leading cause of death worldwide. The aim of this thesis project was to design and optimize imaging agents for the diagnosis and/or therapy of various cancers.The first axis of this thesis focused on the development of a bimodal PET/fluorescence imaging agent capable of targeting neurotensin NTS1 receptors overexpressed in certain cancers. PET imaging would allow efficient detection of tumors and their metastases, while fluorescence imaging would facilitate the evaluation of tumor margins during surgery. Several compounds were synthesized, labelled with gallium-68 and studied in preclinical studies in a pancreatic cancer model. Very promising results were obtained for one compound, making it a good candidate for the diagnosis and fluorescence guided surgery of pancreatic cancer.The second line of research was devoted to the design of a PET radiotracer targeting NTS1. A molecule named [177Lu]Lu-IPN01087 is currently being evaluated in clinical trials for targeted radiotherapy. The identification of a diagnostic companion agent would facilitate the selection of patients eligible for this therapy. We synthesized and evaluated in vivo, in a colorectal cancer model, different gallium-68 labelled tracers, highlighting a potential candidate for the diagnosis by PET imaging of NTS1 overexpressing cancers.Finally, the last part of this thesis focused on the development of a theranostic SPECT/PDT imaging agent targeting the EGFR receptor. SPECT imaging would allow the diagnosis and staging of patients, while the PDT probe would facilitate the surgical resection of the tumor and eradication of cancer cells. We used a trivalent platform, dichlorotetrazine, that allowed us to introduce an indium-111 chelating agent and a photosensitizer via a site-specific bioconjugation reaction on a nanobody. The resulting conjugate was evaluated in vitro and the biodistribution and efficacy of the photodynamic therapy were investigated in preclinical studies.