Roger Schibli, PhD Paul Scherrer Institut, Switzerland
Why is this important?
Despite the effectiveness of PRRT to prolong NET survival, many patients will be diagnosed with metastases a few years later. This two-year Petersen Investigator Project explored the safety of a novel radionuclide for a more effective PRRT treatment. Schibli and colleagues developed a new therapy based on terbium radionuclides (161Tb), which have distinct radioactive properties, compared to Lu 177. The researchers evaluated the improved ability of 161Tb-DOTATOC to kill NET cells in a pre-clinical setting before they proceed with the first-in-man study. They theorize that this new therapy may result in a paradigm shift in the PRRT treatment of NETs
What did researchers do?
Schibli developed a different radionuclide-biomolecule, that uses terbium-161 (161Tb) instead of lutetium-177 (177Lu), bound to DOTATOC. The 161Tb-molecules were then applied to two NET patients in a clinical pilot study to investigate its distribution in the body.
What did researchers learn?
Due to its different radiation-emitting properties, he found that 161Tb-labeled molecules are more effective in killing cancer cells and that killing single cancer cells could represent a paradigm shift in the treatment of neuroendocrine cancer. This may provide patients with a more sustainable therapy option.
Zhang J, Singh A, Kulkarni HR, et al. From bench to bedside—the Bad Berka experience with first-in-human studies. Semin Nucl Med. 2019;49(5):422-437. doi: 10.1053/j.semnuclmed.2019.06.002. Epub 2019 Jul 6.
Gracheva N, Müller C, Talip Z, et al. Production and characterization of no-carrier-added 161Tb as an alternative to the clinically applied 177Lu for radionuclide therapy. EJNMMI Radiopharm Chem. 2019;4(1):12. Published 2019 Jul 10. doi:10.1186/s41181-019-0063-6
What is the next step?
These data will serve as the basis for a clinical study whose success may encourage the use of 161Tb as an improved PRRT therapeutic option.
This NETRF-funded project was successfully performed regarding the following aspects: (i) The production of 161Tb was improved and a scale-up was achieved reproducibly while maintaining the excellent quality of the product; (ii) the production of 161Tb-DOTATOC was set up on an automated synthesis module in a reproducible manner; (iii) the results of the preclinical experiments clearly indicated that 161Tb may be a more favorable option to be used for PRRT than 177Lu. Beyond the original goals, additional preclinical research revealed that DOTA-LM3 may be of great interest to be used with 161Tb because it is a somatostatin receptor antagonist that does not effectively internalize into the cell cytoplasm; (iv) Finally, we were able to demonstrate the first application of 161Tb in a patient worldwide, in a joint endeavor between PSI and Zentralklinik Bad Berka (Prof. Richard Baum). Overall, the results of the research performed are promising and will pave the way towards further clinical exploration of 161Tb for the treatment of patients with NET.
- City: Zurich
- Country: Switzerland
- Grant Duration: 2 years
- Awards: Petersen Investigator Award
- Sponsor: Margie & Robert E. Petersen Foundation
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.