PhD student in Radiopharmaceutical Sciences - #56467

Job Description

Lung neuroendocrine tumors (NETs), including pulmonary carcinoids and large cell neuroendocrine carcinoma (LCNEC), are rare tumors and with limited treatment options and poor survival rates in metastatic disease. Although systemic therapies remain the mainstay of treatment, they offer limited benefit to lung NET patients. Therefore, there is a critical need for targeted strategies enabling both accurate tumor visualization and effective therapy. DLL3 (Delta-like ligand 3) is a transmembrane protein aberrantly expressed in 50% of (metastatic) lung NETs and 65% of LCNEC and minimally expressed in normal adult tissues, making it an ideal target for selective tumor targeting. Recent studies have shown remarkable response rates utilizing T-cell engagers targeting DLL3 in these tumors, but considering the DLL3 heterogeneity PET-imaging will be useful for patient selection.

Receptor targeted radionuclide imaging and therapy was discovered and pioneered at Erasmus MC. This therapy is currently being applied worldwide in the management of neuroendocrine tumors that are somatostatin receptor (SSTR) positive. DLL3 targeting has the same potential, however, no clinically validated DLL3-targeting radiotracers currently exist.

The overall goal of this proposal is therefore to develop high affinity DLL3-binding peptides using DNA-encoded libraries, and to optimize them as radiolabeled agents for both positron emission tomography (PET) imaging and targeted radionuclide therapy (TRT). We hypothesize that DLL3- targeted radioligands will improve diagnostic accuracy and provide a novel therapeutic modality, which could transform clinical management and improve survival outcomes of patients with lung NETs. Beyond NETs multiple other tumors express DLL3. Hence, this translational PhD project has the potential to develop a new kind of therapy with an significant clinical impact.