161Tb-PSMA: a promising alternative for the treatment of prostate cancer

Project summary

This project is based on a novel collaboration between TerThera B.V. and Erasmus MC. This partnership creates a unique situation and enables the opportunity to use a newly produced therapeutic radioisotope (terbium-161) with a molecule used for the treatment of prostate cancer (PSMA) creating the radiopharmaceutical 161Tb-PSMA. 161Tb-PSMA is an anticancer agent and specifically bind to prostate cancer cells. Here, we will optimize 161Tb-PSMA production and perform the first safety assessment in patients. Additionally, we will perform preclinical studies to compare 161Tb-PSMA with the currently used 177Lu-PSMA.

Multiple lutetium-177 based radiopharmaceuticals have been registered and this resulted in a world-wide shortage of lutetium-177. This became evident in November-December 2022, when for over six weeks no lutetium-177 was delivered to Erasmus MC leading to long delays in, sometimes critically important, treatment of oncological patients. Terbium-161 is a viable alternative for lutetium-177 as it has near-identical radiochemical properties. The new Dutch company TerThera possesses a large quantity of Gd-160, the precursor for Terbium-161, and has started providing Tb-161 for the development and production of radiopharmaceuticals.

In this project 161Tb-PSMA will be synthesized and optimized toward clinical use. Meanwhile fundamental research will be performed by zooming in onto the comparison between lutetium-177 and terbium-161 labeled PSMA will be made.  The final radiopharmaceutical formulation will be used to perform a Phase I clinical trial to establish the maximum safe activity as well as first indicators of efficacy of Tb-PSMA for the treatment of castration resistant prostate cancer.

Overall, with the obtained result, TerThera will be able to further develop Tb-161 as an active pharmaceutical ingredient.  There will be a better fundamental understanding on why Tb-161 is an effective radioisotope for cancer treatment. By performing the clinical study, we will create an alternative option to be able to treat more oncological patients.