Purpose: Targeted Radionuclide Therapy and, in particular, Targeted Alpha Therapy (TAT) are emerging as effective treatment strategies for various cancers. Radiopharmaceuticals based on Â²Â²â?µAc (half-life 9.92 days) especially, have shown promising therapeutic effects when other options were not effective (e.g. surgery, chemotherapy or external beam therapy). However, development and clinical trials involving Â²Â²â?µAc radiopharmaceuticals are hindered due to the limited availability of the radionuclide. At TRIUMF, the infrastructure exists to produce several GBq of Â²Â²â?µAc (thousands of patient doses) more than once a month, as well as other potential TAT radionuclides such as Â²Â¹Â³Bi (45.6 min), Â²Â¹Â²Pb (10.6 h), and Â²Â¹Â²Bi (60.6 min). This will enable and accelerate the development of TAT radiopharmaceuticals.
Methods: Naturally enriched Â²Â³Â²Th is encapsulated in a target holder and installed in the TRIUMF Isotope Irradiation Facility (IPF). The target is irradiated with 480 MeV protons at beam currents of up to 100 ÂµA, undergoing spallation and co-producing hundreds of isotopes. The target is then removed and processed to isolate and purify the desired Â²Â²â?µAc, which can also be used as a generator for Â²Â¹Â³Bi. Co-production of Â²Â²â?¸Th (1.9 y) during the spallation process also provides a generator of Â²Â¹Â²Pb and Â²Â¹Â²Bi.
Results: First test irradiations demonstrated that over 500 MBq of Â²Â²â?µAc can be produced in a 36-hour irradiation. Furthermore, almost 90 MBq of Â²Â²â?µRa (14.9 d) are produced, which can be utilized into a Â²Â²â?µRa/Â²Â²â?µAc generator. By only using the Â²Â²â?µAc from the decay of Â²Â²â?µRa, we greatly reduce the long-lived and chemically inseparable Â²Â²â?·Ac contaminant (21.77 years).
Conclusion: At TRIUMF, we are able to produce large quantities of Â²Â²â?µAc for TAT. By utilizing the parent isotope Â²Â²â?µRa, the end-product purity is greatly increased. This will enable the accelerated development of optimized Â²Â²â?µAc based radiopharmaceuticals and the implementation of TAT in clinical practice.