Development and Characterization of 3D Spheroids for Targeted Radiopharmaceutical Therapy
Background and Rationale
Despite rapid advances in modern medicine and substantial improvements in survival rates of many cancers, pancreatic cancer remains an extremely deadly disease with a five-year survival rate of less than 15%. Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent type of pancreatic cancer and develops in the exocrine compartment of the pancreas. To improve patient prognosis, there is an urgent need for the development of new strategies for early detection of the disease as well as more targeted and effective treatments. In this regard, targeted radionuclide therapy (TRT) can provide a step towards personalized and precise medicine, with research showing significant improvements in patient outcomes. TRT is a systemic treatment that employs radiopharmaceuticals that target the tumor on a cellular level by exploiting tumor-specific biomarkers that are overexpressed on the surface of cancerous cells. With these radiopharmaceuticals, TRT aims to deliver potent radiation directly to the primary tumor and its metastasis with minimal collateral damage to normal tissues.
Carbonic anhydrase IX (CA IX) is a membrane-bound enzyme overexpressed in hypoxic tumour regions, including PDAC, making it a promising target for TRT. To evaluate CA IX-targeted radiopharmaceuticals preclinically, reliable models are needed that reflect the hypoxic regulation of CA IX. While traditional 2D monolayer cell cultures are unable to mimic tumour complexity and hypoxia gradients, three-dimensional (3D) spheroid models provide a more biologically relevant in vitro environment, better reflecting the tumour’s structural organisation and the development of hypoxic regions where CA IX is upregulated.
Objectives
The goal of this internship is to develop and characterize a reproducible 3D PDAC spheroid model that mimics the hypoxic tumour microenvironment. These spheroids will serve as a tool for downstream therapeutic research targeting CA IX.