Scientists will explore a novel, very stable compound that binds to NET cells’ somatostatin receptors (SSTR2) more tightly than lutetium 177 (Lu-177) dotatate. This new radiopharmaceutical will be compared with Lu-177 dotatate in disease models. Researchers hope tighter binding of this radiotherapeutic agent to cancer cell receptors will lead to higher radiation accumulation and improved cancer response.
What question(s) will researchers ask?
Is there a way to improve the binding of radiotherapeutic agents to neuroendocrine tumor (NET) cells to enhance radiation exposure during Peptide Receptor Radionuclide Therapy (PRRT)?
Why is this important?
While PRRT is an effective treatment for many patients, not everyone responds equally well. Principal investigator Kuo-Shyan Lin, PhD, BC Canada, says he thinks a low response in some patients may be due to an ineffective interaction between the radiotherapeutic agent and the tumor cells. Lin believes that loose, unstable tumor cell-binding of the drug may be partly to blame. The first FDA-approved PRRT agent binds to the somatostatin receptors on the surface of NET cells. Dr.Lin says a tighter, stronger binding of the drug to those receptors could increase the killing potency of its radiation, helping improve the treatment response to PRRT.
What will researchers do?
Dr. Lin will use a new kind of small molecule for the design of radiotherapeutic agents which bind more tightly to the somatostatin receptors found on NET cells.
Testing a novel agent as an imaging tracer
First, researchers at Dr. Lin’s laboratory will try to attach an imaging radio-tag to the small molecule, which Lin hopes will bind the somatostatin receptor, and allow its location and distribution within the body to be tracked by PET scan. Unlike the radiotherapeutic agents, the radio-tag on the imaging agents allows the visualization of the small molecule but does not effectively kill cells. He will inject the imaging agent into tumor-bearing mice and use PET scans to show how well the agent targets and binds to NET cells. This will be monitored by its accumulation in the animal’s tumors.
Testing novel agent as a possible treatment
If the first tests are successful and improved cell binding is observed, the researchers will replace the imaging radio-tag with a radiotherapeutic component and evaluate the new radiotherapeutic agent’s cancer-cell killing effectiveness in tumor-bearing mice.
How might this research affect NET treatment in the future?
Dr. Lin hopes his research could contribute to the discovery of a novel class of radiotherapeutic agents that more effectively bind and treat NETs.
What is the next step?
If Dr. Lin’s concept shows feasibility, it would then undergo comprehensive laboratory testing to look for toxicity and other side effects. If extensive laboratory studies show it is safe to test in humans, it would advance into clinical trials, a three-phased regulated series of studies in increasingly larger patient pools to generate the data needed to apply for drug approval.
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.