Actinium-225

Actinium-225 (²²⁵Ac, Ac-225) is an isotope of actinium. It undergoes alpha decay to francium-221 with a half-life near 10 days, and is an intermediate decay product in the neptunium series (the decay chain starting at ²³⁷Np). Except for minuscule quantities arising from this decay chain in nature, ²²⁵Ac is entirely synthetic.

The decay properties of actinium-225 (emitting four alpha particles within about an hour) are favorable for usage in targeted alpha therapy (TAT); clinical trials have demonstrated the applicability of radiopharmaceuticals containing ²²⁵Ac to treat various types of cancer. However, the scarcity of this isotope resulting from its necessary synthesis in cyclotrons limits its potential applications. Another such isotope, bismuth-213, is produced necessarily (given its short half-life) from the decay of actinium-225 in a generator and immediate use; it gives only the last of the four alpha particles, requiring a larger amount of actinium, but may be preferred if available.

Decay and occurrence

Actinium-225 decays exclusively by alpha emission. It is part of the neptunium series, for it arises as a decay product of neptunium-237 and its daughters such as uranium-233 and thorium-229. It is the last nuclide in the chain with a half-life over a day until the penultimate product, bismuth-209 (half-life years). The final decay product of ²²⁵Ac is stable ²⁰⁵Tl.

As a member of the neptunium series, it does not occur in nature except as a product of trace quantities of ²³⁷Np and its daughters formed by neutron capture reactions on primordial ²³²Th and ²³⁸U. It is much rarer than ²²⁷Ac and ²²⁸Ac, which respectively occur in the decay chains of uranium-235 and thorium-232. Its abundance was estimated as less than relative to ²³²Th and around relative to ²³⁰Th in secular equilibrium.

Discovery

Actinium-225 was discovered in 1947 as part of the hitherto unknown neptunium series, which was populated by the synthesis of ²³³U. A team of physicists from Argonne National Laboratory led by F. Hagemann initially reported the discovery of ²²⁵Ac and identified its 10-day half-life. Independently, a Canadian group led by A. C. English identified the same decay scheme; both papers were published in the same issue of Physical Review.

Production

As ²²⁵Ac does not occur in any appreciable quantities in nature, it must be synthesized in specialized nuclear reactors or accelerators. The majority of ²²⁵Ac results from the alpha decay of ²²⁹Th, but this supply is limited because the decay of ²²⁹Th (half-life 7920 years) is slow. It is also possible to breed ²²⁵Ac from radium-226 in the ²²⁶Ra(p,2n) reaction. This was first done in 2005, though the production and handling of ²²⁶Ra are difficult because of the respective cost of extraction and hazards of decay products such as radon-222. Alternatively, ²²⁵Ac can be produced in spallation reactions on a ²³²Th target irradiated with high-energy proton beams. Current techniques enable the production of millicurie quantities of ²²⁵Ac; however, it must then be separated from other reaction products. This is done by allowing some of the shorter-lived nuclides to decay; actinium isotopes are then chemically purified in hot cells and ²²⁵Ac is concentrated. Special care must be taken to avoid contamination with the longer-lived beta-emitting actinium-227.

For decades, most ²²⁵Ac was produced in one facility—the Oak Ridge National Laboratory in Tennessee—further reducing this isotope's availability even with smaller contributions from other laboratories. Additional ²²⁵Ac is now produced from ²³²Th at Los Alamos National Laboratory and Brookhaven National Laboratory. The TRIUMF facility and Canadian Nuclear Laboratories have formed a strategic partnership around the commercial production of actinium-225.

The limited supply of ²²⁵Ac limits its use in research and cancer treatment. It is estimated that the current supply of ²²⁵Ac only allows about a thousand cancer treatments per year.

Applications

Alpha emitters such as actinium-225 are favored in cancer treatment because of the short range (a few cell diameters) of alpha particles in tissue and their high energy, rendering them highly effective in targeting and killing cancer cells—specifically, alpha particles are more effective at breaking DNA strands. The 10-day half-life of ²²⁵Ac is long enough to facilitate distribution, but short enough that little remains in the body months after treatment. Additionally, each decay of ²²⁵Ac to ²⁰⁹Bi nets four high-energy alpha particles, greatly increasing its potency.

Despite its limited availability, several clinical trials have been completed, demonstrating the effectiveness of ²²⁵Ac in targeted alpha therapy. Complexes including ²²⁵Ac—such as antibodies labeled with ²²⁵Ac—have been tested to target various types of cancer, including leukemia, prostate carcinoma, and breast carcinoma in humans. For example, one experimental ²²⁵Ac-based drug has shown effectiveness against acute myeloid leukemia without harming the patient. Further clinical trials of other drugs are underway such as the SatisfACtion trial (NCT04597411), a Phase I/II, open-label, multi-center study that is evaluating 225Ac-PSMA-R2 in patients with metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic castration-resistant prostate cancer (mCRPC).

References