PhD Position in Radiopharmaceutical Sciences: Claudin-targeted radiotheranostic peptides for precision imaging and therapy of pancreatic ductal adenocarcinoma

Doctorat / PhD Profil chercheur : First Stage Researcher (R1) Type de contrat : Temporary Date limite de candidature : 30 Nov 2026 - 23:59 (Europe/Madrid) Date de début : 1 Feb 2027 Programme UE : Not funded by a EU programme Département : Instituto de Investigaciones Biomédicas Sols-Morreale (Consejo Superior de Investigaciones Científicas [CSIC]/Universidad Autónoma de Madrid [UAM]) Domaine : Medical sciences

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies worldwide, with a five-year survival rate of just 11%. Late diagnosis, early metastatic dissemination, dense stromal desmoplasia, and intrinsic resistance to conventional chemo- and radiotherapy severely limit current treatment outcomes. Despite advances in surgical management and systemic therapies, effective, tumour-specific therapeutic strategies remain an urgent unmet need. Targeted radionuclide therapy (TRT) has emerged as a promising modality in precision oncology by combining the cytotoxic effects of radiotherapy with the specificity of molecularly targeted ligands. When integrated with molecular imaging, TRT enables radiotheranostics, offering simultaneous tumour localisation, molecular characterisation and real-time assessment of therapeutic response. Peptide-based vectors are particularly suitable for this approach due to their favourable pharmacokinetics, high tumour penetration, minimal immunogenicity, and chemical flexibility, allowing rational optimisation for enhanced specificity and binding affinity. A critical factor for TRT efficacy is the choice of an optimal molecular target. Claudin-4 and claudin-18.2, two tight junction proteins, are frequently overexpressed in PDAC while absent or minimally expressed in normal pancreatic tissue. Their high prevalence, tumour-restricted localisation and accessible extracellular loops make them ideal candidates for peptide-based radiotheranostics. Current therapeutic strategies targeting these claudins, including monoclonal antibodies and antibody-drug conjugates, are limited by poor tumour penetration, slow pharmacokinetics, immunogenicity and high production costs. While the C-terminal fragment of Clostridium perfringens enterotoxin (cCPE) provides a promising scaffold for claudin-4 targeting, existing variants demonstrate insufficient in vivo tumour retention and rapid clearance, and no peptide ligands have yet been developed for claudin-18.2. The CLAUDIN-RT project aims to develop next-generation peptide radioligands targeting claudin-4 and claudin-18.2 for radiotheranostic applications. We will pursue two complementary strategies: (1) rational redesign of the cCPE scaffold using advanced structural and computational modelling to optimise binding affinity, specificity, and pharmacokinetics for claudin-4; and (2) identification of high-affinity, selective peptide ligands for claudin-18.2 through phage display technology combined with computational analysis. Selected ligands will be modified for…