43/47Scandium-DOTATATE: A Next-Generation Theranostics Pair to Diagnose and Treat
Neuroendocrine Tumors by Image-Guided Assessment

Can building a theranostics pair using the same element increase stability and efficacy
in NETs?

Neuroendocrine tumors (NETs) are a rare form of cancer that originate in the pancreas, thyroid, small intestines and lung. The incidence of these tumors has been steadily rising and often patients are diagnosed at an advanced stage and are incurable. Dr. Keutgen proposes attacking these tumors with “Theranostics” a therapeutic that combines radioactive isotopes that diagnose and help locate cancers with radioactive isotopes that provide therapy and kill cancers. One isotope lights up the cancer,
making it easier to image, and the other delivers radiation directly into the tumors, without damaging non-cancerous cells. NETs are particularly well suited for this novel approach as they express a receptor on the tumor cell surface, allowing for theranostic targeting. Previous clinical trials suggested that the combination of the radioactive elements Gallium-68 for diagnosis and Lutetium-177 for treatment of patients with NETs might be a promising pair, but they have failed to live up to that promise.

Dr. Keutgen proposes to develop a next-generation and improved theranostic pair for NETs, by using two radioisotopes of the same element for diagnosis (Scandium-43) and for treatment (Scandium-47). Using the same element has several advantages including easier production and delivery to hospitals. Moreover, using this novel theranostic pair also allows for the possibility of “adaptive therapy”, using Scandium-47 not only to kill cancer cells but also to direct image-guided assessments after each
dose is given, allowing for “real-time” adjustments to maximize treatment efficacy. Additionally, Dr. Keutgen has identified a novel and promising radiosensitizer called Fulvestrant, thanks in part to his previous Cancer Research Foundation Young Investigator Award, which is currently being used as a hormone blocker in breast cancer treatment. This project will further evaluate whether Fulvestrant increases the effectiveness of Scandium-47 at killing cancer cells when compared to the current standard of care. Together, the radiosensitizer and the theranostic pair have the potential to make a real difference in NET treatment.