Jobid=628549840449315777 (0.0997)
DLL3-targeting peptides for imaging and therapy of lung neuroendocrine tumors (NETs).
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.
Work environment
A healthy population and excellence in healthcare through research and education. This is what Erasmus MC stands for. Conducting groundbreaking work, pushing boundaries and leading the way in research, education, and healthcare. We are practical people with a high level of expertise, working hard to improve and renew the healthcare of today and the public health of tomorrow.
The candidate will be positioned at the department of Radiology and Nuclear Medicine. Our department is known for its forefront research and its state-of-the-art facilities. The concept of peptide receptor radionuclide therapy (PRRT) was introduced in our department and several theranostic agents were developed and tested from bench-to-bedside. The candidate will be a member of the RadioPharmaceutical Chemistry group and will work in collaboration with the department of Pulmonology and Pathology on neuroendocrine tumors of the lung, molecular imaging and targeted radiotherapy.
Qualifications and skills
Applications are invited from enthusiastic and talented young researchers with an active interest in tracer development and translational radiopharmaceutical research.
- MSc in Pharmaceutical Sciences, Medicinal Chemistry or similar.
- Strong knowledge of modern bioorganic chemistry and analytical techniques.
- Experience with DNA-encoded library platform would be an asset.
- You have excellent command of English, both spoken and written.
- Must be able to multitask and thrive in a multidisciplinary, result-oriented environment.
- The ability to improve established methods and explore new lab workflows.
These criteria are considered advantages, but not requirements:
- Previous experience in handling radioactivity and performing radiolabeling procedures.
- Practical experience with cell culture and in vitro assays.
- Experience in molecular docking.
- Familiar with in vivo biological studies.
Terms of employment
- You will receive a temporary position for 4 years.
- The gross monthly salary amounts a minimum of € 3.217,- and a maximum of € 4.077,- (scale OIO).
- Excellent fringe benefits, such as a 13th month that is already paid out in November and an individual travel expense package.
- An International Office which aids you in preparing for you arrival and stay.
- Pension insurance with ABP. We take care of approximately 2/3 of the monthly contribution.
- Special benefits, such as an incompany physiotherapist and bicycle repairer. And there is also a gym where you can work on your fitness after work.
More information
Make this job your next career move! Apply now using the application button. It all starts with taking action.
Do you have questions about the role? Feel free to reach out to Dr. Yann Seimbille, Head of RadioPharmaceutical Chemistry and Associate Professor, via phone.
Your application must include the following documents:
- Curriculum Vitae (including two references willing to provide a recommendation letter on enquiry).
- Motivation letter (maximum of 1 page).
- Copy of your academic MSc grade transcripts and degree certificate.
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