3_at_ORNL_by_Dr_Andrew_R_Burgoyne.jpg) Cherenkov radiation from a sample of Ac-225 (17 mCi) | |
| General | |
|---|---|
| Symbol | 225Ac |
| Names | actinium-225 |
| Protons(Z) | 89 |
| Neutrons(N) | 136 |
| Nuclide data | |
| Natural abundance | trace |
| Half-life(t1/2) | 9.919 d[1] |
| Isotope mass | 225.023229[2]Da |
| Excess energy | 21637±5keV |
| Parent isotopes | 225Ra (β−) 229Pa (α) 225Th (EC) |
| Decay products | 221Fr |
| Decay modes | |
| Decay mode | Decay energy (MeV) |
| α | 5.935[3] |
| Isotopes of actinium Complete table of nuclides | |
Actinium-225 (225Ac,Ac-225) is anisotope ofactinium. It undergoesalpha decay tofrancium-221 with ahalf-life near 10 days, and is an intermediate decay product in theneptunium series (thedecay chain starting at237Np). Except for minuscule quantities arising from this decay chain in nature,225Ac is entirelysynthetic.
The decay properties of actinium-225 (emitting four alpha particles within about an hour) are favorable for usage intargeted alpha therapy (TAT); clinical trials have demonstrated the applicability ofradiopharmaceuticals containing225Ac to treat various types ofcancer. However, the scarcity of this isotope resulting from its necessary synthesis incyclotrons limits its potential applications. Another such isotope,bismuth-213, is produced necessarily (given its short half-life) from the decay of actinium-225 in agenerator 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.
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Actinium-225 decays exclusively byalpha emission. It is part of theneptunium series, for it arises as adecay product ofneptunium-237 and itsdaughters such asuranium-233 andthorium-229. It is the lastnuclide in the chain with a half-life over a day until the penultimate product,bismuth-209 (half-life2.01×1019 years).[1] The final decay product of225Ac isstable205Tl.
As a member of the neptunium series, it does not occur in nature except as a product of trace quantities of237Np and its daughters formed byneutron capture reactions onprimordial232Th and238U.[4] It is much rarer than227Ac and228Ac, which respectively occur in thedecay chains ofuranium-235 andthorium-232. Its abundance was estimated as less than1.1×10−19 relative to232Th and around9.9×10−16 relative to230Th insecular equilibrium.[4]
Actinium-225 was discovered in 1947 as part of the hitherto unknown neptunium series, which was populated by the synthesis of233U.[5] A team of physicists fromArgonne National Laboratory led by F. Hagemann initially reported the discovery of225Ac and identified its 10-day half-life.[6] Independently, a Canadian group led by A. C. English identified the same decay scheme; both papers were published in the same issue ofPhysical Review.[5][7][8]
As225Ac does not occur in any appreciable quantities in nature, it must be synthesized in specialized nuclear reactors or accelerators. The majority of225Ac results from the alpha decay of229Th, but this supply is limited because the decay of229Th (half-life 7920 years[1]) is slow.[9] It is also possible to breed225Ac fromradium-226 in the226Ra(p,2n) reaction. This was first done in 2005, though the production and handling of226Ra are difficult because of the respective cost of extraction and hazards of decay products such asradon-222.[9]Alternatively,225Ac can be produced inspallation reactions on a232Th target irradiated with high-energyproton beams.[10] Current techniques enable the production ofmillicurie quantities of225Ac; however, it must then be separated from other reaction products.[11] This is done by allowing some of the shorter-lived nuclides to decay; actinium isotopes are then chemically purified in hot cells and225Ac is concentrated. Special care must be taken to avoid contamination with the longer-livedbeta-emittingactinium-227.[10]
For decades, most225Ac was produced in one facility—theOak Ridge National Laboratory in Tennessee—further reducing this isotope's availability even with smaller contributions from other laboratories.[10] Additional225Ac is now produced from232Th atLos Alamos National Laboratory andBrookhaven National Laboratory.[12] TheTRIUMF facility andCanadian Nuclear Laboratories have formed a strategic partnership around the commercial production of actinium-225.[13]
The limited supply of225Ac limits its use in research andcancer treatment. It is estimated that the current supply of225Ac only allows about a thousand cancer treatments per year.[9][14]
Alpha emitters such as actinium-225 are favored in cancer treatment because of the short range (a fewcell diameters) of alpha particles intissue and their high energy, rendering them highly effective in targeting and killingcancer cells—specifically, alpha particles are more effective at breakingDNA strands. The 10-day half-life of225Ac is long enough to facilitate distribution, but short enough that little remains in the body months after treatment.[12] Additionally, each decay of225Ac to209Bi nets four high-energy alpha particles, greatly increasing its potency.[12][15]
Despite its limited availability, several clinical trials have been completed, demonstrating the effectiveness of225Ac in targeted alpha therapy.[10][15] Complexes including225Ac—such as antibodies labeled with225Ac—have been tested to target various types of cancer, includingleukemia,prostate carcinoma, andbreast carcinoma in humans.[15] For example, one experimental225Ac-based drug has shown effectiveness againstacute myeloid leukemia without harming the patient. Further clinical trials of other drugs are underway such as theSatisfACtion trial (NCT04597411), a Phase I/II, open-label, multi-center study that is evaluating225Ac-PSMA-R2 in patients withmetastatic hormone-sensitive prostate cancer (mHSPC) andmetastatic castration-resistant prostate cancer (mCRPC).[12][16]