Project title: uPAR-targeted PRRT: new radionuclide-based therapy
Andreas Kjaer, MD, PhD, DMSc Copenhagen University Hospital
- Status: Completed
- Year(s): 2020
- Grant Type: Investigator
- Research Type: Translational
- Primary Tumor Site: Multiple
- Area of Inquiry: Targeted radionuclide therapy (theranostics)
Description
Dr. Kjaer will develop a new targeted radionuclide therapy based on the urokinase-type plasminogen activator receptor (uPAR), which is found in the tumor cells of most neuroendocrine tumor patients, including in patients with G3/neuroendocrine carcinomas.
What question will you try to answer through your research?
A major problem with the current somatostatin receptor targeting radionuclide therapy (SSR-PRRT) is its ineffectiveness on patients with no or low somatostatin receptor expression. If successful, our new technology would circumvent this problem by targeting a different receptor molecule, broadening the number of patients who can receive targeted radionuclide therapy.
Why is this important?
Targeted radionuclide therapy using the somatostatin receptor has proven to be a valuable treatment for NET patients. However, in many cases, the somatostatin receptor expression is too low for the use of SSR-PRRT, such as in patients with the more aggressive NET (NEC/G3). By developing a radionuclide therapy targeting uPAR we hope to provide another targeted radionuclide therapy that may benefit these patients.
What will you do as part of this research project?
Based on our proof-of-concept study on radionuclide therapy that targets uPAR, we will develop the next generation of our uPAR ligand. We will then test whether it can work in relevant NET/NEC animal models without deleterious side effects before preparing for clinical translation.
How might your research improve the treatment of NETs?
We hope that our approach will ultimately broaden the applicability of targeted radionuclide therapy in patients with NETs. In addition, since uPAR expressing cells are the most aggressive cancer cells, the therapy may also prove to be highly effective in treating patients with these tumors.
What is your next step?
After we complete this study, our next step would be to work to translate our findings into human studies and clinical care.
Outcomes:
We have now completed and published the clinical trial that demonstrates that PRRT targeted towards the target uPAR is promising. Many patients not eligible for current PRRT (targeting the somatostatin receptor, e.g. Lutathera) have uPAR expressed and therefore potentially may be eligible for uPAR-PRRT as an alternative. We are progressing in our work toward making an effective uPAR-PRRT drug.
Additional Details
- City: Copenhagen
- Country: Denmark
- Grant Duration: 2 years
- Awards: Investigator
DISCLAIMER
NETRF funds laboratory research to understand the development of neuroendocrine tumors and translational research to explore new concepts in treatment. Research grant descriptions and research updates from NETRF are not intended to serve as medical advice. It can take years for research discoveries to be fully validated and approved for patient care. Always consult your health care providers about your treatment options.