161Tb-labeled radiopharmaceuticals targeting mucin receptors for treatment of pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadliest cancers worldwide with a five-year survival rate of less than 10%. To improve patient prognosis, there is an urgent need for the development of more effective therapeutic strategies. Targeted radionuclide therapy (TRNT) is an established, evidence-based treatment modality where a radioactive ligand (i.e. radiopharmaceutical) is injected intravenously allowing targeted irradiation of the primary tumor and all its metastasis that express the molecular target. When a diagnostic radionuclide is used, the radiopharmaceutical can be used for imaging applications. Mucin 1 is one of the most important tumor biomarkers and an attractive target for antibody-based therapies as it is aberrantly overexpressed in various carcinomas, including more than 90% of PDAC. This study aims to develop highly selective radiopharmaceuticals targeting the C-terminal domain of mucin 1, radiolabeled with radionuclides terbium-161 (therapeutic) or terbium-152/155 (diagnostic) to efficiently treat and image highly malignant PDAC.