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(Wednesday, 7/17/2019) 4:30 PM - 6:00 PM
Room: 304ABC
Purpose: Targeted Radionuclide Therapy and, in particular, Targeted Alpha Therapy (TAT) are emerging as effective treatment strategies for various cancers. Radiopharmaceuticals based on ²²⁵Ac (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 ²²⁵Ac radiopharmaceuticals are hindered due to the limited availability of the radionuclide. At TRIUMF, the infrastructure exists to produce several GBq of ²²⁵Ac (thousands of patient doses) more than once a month, as well as other potential TAT radionuclides such as ²¹³Bi (45.6 min), ²¹²Pb (10.6 h), and ²¹²Bi (60.6 min). This will enable and accelerate the development of TAT radiopharmaceuticals.
Methods: Naturally enriched ²³²Th 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 µA, undergoing spallation and co-producing hundreds of isotopes. The target is then removed and processed to isolate and purify the desired ²²⁵Ac, which can also be used as a generator for ²¹³Bi. Co-production of ²²⁸Th (1.9 y) during the spallation process also provides a generator of ²¹²Pb and ²¹²Bi.
Results: First test irradiations demonstrated that over 500 MBq of ²²⁵Ac can be produced in a 36-hour irradiation. Furthermore, almost 90 MBq of ²²⁵Ra (14.9 d) are produced, which can be utilized into a ²²⁵Ra/²²⁵Ac generator. By only using the ²²⁵Ac from the decay of ²²⁵Ra, we greatly reduce the long-lived and chemically inseparable ²²⁷Ac contaminant (21.77 years).
Conclusion: At TRIUMF, we are able to produce large quantities of ²²⁵Ac for TAT. By utilizing the parent isotope ²²⁵Ra, the end-product purity is greatly increased. This will enable the accelerated development of optimized ²²⁵Ac based radiopharmaceuticals and the implementation of TAT in clinical practice.
Keywords
Targeted Radiotherapy, Alpha-particles, Cyclotrons
Taxonomy
IM/TH- Radiopharmaceutical therapy: radiation chemistry and radiopharmaceutical development
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