Actinides: Radiation for Remission
By Noah Bussell
Take neptunium, plutonium, and actinium—these “things” may sound fake, or perhaps it seems that they belong alongside the jargon of a Madeleine L’Engle novel. However, these are actually a few of the rare and radioactive elements known as “actinides” (sometimes referred to as f-block elements because of their location on the periodic table). (1) As one might expect, they are quite exotic—relativistic effects must often be considered when studying actinides, effects which only become pronounced in extreme environments, such as in the vicinity of black holes.(2) (3)While the actinides are likely unfamiliar to most outside of the scientific community, a select few, such as uranium, often populate science fiction media and, lamentably, the reality of the not-so-distant past and present. (4)Nonetheless, scientists are developing chemical compounds that incorporate actinides into their molecular structure in order to leverage their radioactive properties for medical purposes such as cancer treatment.
This is quite the ambitious task and rightfully comes across as a bit unreasonable. Actinides are unstable and thus challenging to characterize, thereby making it difficult to utilize them in cancer therapies. Nonetheless, the same properties, namely radioactivity, that make them dangerous also make them useful in the clinic. Unfortunately, these elements are still somewhat of a black box. To manage their usage in the clinic, scientists must understand the physical and chemical properties of the actinides and engineer actinide-containing biological complexes. (6) This developing research contributes to efforts in the synthesis of radiopharmaceuticals, which are a novel class of drugs that deliver radiation directly to tumor cells. (7)
A study conducted by the Abergel Group at the University of California, Berkeley, for instance, published in Nature this year, characterized some properties of an Einsteinium complex for the first time. (8) (9) By using an assortment of X-ray spectroscopy techniques, researchers in the group were able to measure properties like chemical bond distances and oxidation states. Also, by developing methods for working with such unstable complexes and establishing comparisons with other actinides, the group is paving the way for future studies to understand the properties of these elements and how they can then be utilized in the clinic and beyond.
Within the context of oncology then, radiopharmaceuticals composed of an actinide element, a targeting molecule, and a component that links the two can be synthesized for treatments (10). By emitting alpha radiation at the site of a tumor, these actinide complexes can induce positive outcomes in cancer patients.
A 2018 study, conducted by researchers in South Africa and Germany, showed that this technology could actually be utilized to achieve remission in patients with advanced metastatic prostate cancer with limited side effects. (11)The drug they used, 225Ac-prostate-specific membrane antigen (PSMA)-617, works by targeting prostate-specific membrane antigen (PSMA) which is overexpressed on the surface of cancer cells. (12) Once 225Ac-PSMA-617 is bound to PSMA and thus the cancer cell, Ac-255 emits multiple high-energy alpha particles along its “decay chain,” effectively suppressing tumor cells that many conventional cancer therapies cannot. (13) (PSMA)-617 also minimizes treatment toxicity because the short range of alpha radiation (a few cell diameters) can be specifically targeted to cancer cells. In the research group’s analysis, 7 (41%) of the 17 patients in the study experienced remission while the disease had stabilized in another 7 patients.
Nonetheless, these actinide elements can be difficult to produce. This limited availability can incite substantial costs, so widespread availability of this type of treatment is likely far off—although researchers are currently developing methods to more effectively synthesize Ac-255. (14) With cancer often disproportionately affecting communities of color and low income communities, (15) it is essential that treatments are made available to all cancer patients, and not only those who can afford treatment.
So, while the science is still in development, and numerous obstacles remain for scientists to navigate, research groups across the world are beginning to understand the inner workings of actinides and the molecules that they form. Beyond just the chemical issues surrounding the project, scientists, public health experts, and teams of other professionals will need to find ways to make such exotic treatments accessible to not only tackle the disease itself, but also the inequities surrounding cancer and its treatment as a whole. Regardless, we just may soon have new, innovative ways to widely use sci-fi-esque molecules for a practical and necessary cause.
- Chemistry LibreTexts. (2015, May 22). General properties and reactions of the actinides. https://chem.libretexts.org/Bookshelves/Inorganic_Chemistry/Modules_and_Websites_(Inorganic_Chemistry)/Descriptive_Chemistry/Elements_Organized_by_Block/4_f-Block_Elements/The_Actinides/1General_Properties_and_Reactions_of_The_Actinides
- Marsh, M. L., White, F. D., Galley, S. S., & Albrecht-Schmitt, T. E. (2018). Comparison of the electronic properties of f7, f8, and f9 lanthanides with formally isoelectronic actinides. In J.-C. G. Bünzli & V. K. Pecharsky (Eds.), Handbook on the Physics and Chemistry of Rare Earths (Vol. 53, pp. 1–33). Elsevier. https://doi.org/10.1016/bs.hpcre.2018.01.001
- Zhang, X. (2005). Relativistic astrophysics around black holes [Doctoral dissertation, The University of Alabama in Huntsville]. ProQuest Dissertations Publishing. http://adsabs.harvard.edu/abs/2005PhDT………7Z
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- National Aeronautics and Space Administration Jet Propulsion Laboratory. (2016, April 12). Spacecraft power for cassini—fact sheet. NASA Science Solar System Exploration. https://solarsystem.nasa.gov/resources/17327/spacecraft-power-for-cassini-fact-sheet
- BioActinide Chemistry Group @ Berkeley. (n.d.). Research. Berkeley Lab. https://abergel.lbl.gov/research/
- Sgouros, G., Bodei, L., McDevitt, M. R., & Nedrow, J. R. (2020). Radiopharmaceutical therapy in cancer: Clinical advances and challenges. Nature Reviews Drug Discovery, 19(9), 589–608. https://doi.org/10.1038/s41573-020-0073-9
- Carter, K. P., Shield, K. M., Smith, K. F., Jones, Z. R., Wacker, J. N., Arnedo-Sanchez, L., Mattox, T. M., Moreau, L. M., Knope, K. E., Kozimor, S. A., Booth, C. H., & Abergel, R. J. (2021). Structural and spectroscopic characterization of an einsteinium complex. Nature, 590(7844), 85–88. https://doi.org/10.1038/s41586-020-03179-3
- Chao, J. (2021, February 3). Discoveries at the Edge of the Periodic Table: First Ever Measurements of Einsteinium. Berkeley Lab. https://newscenter.lbl.gov/2021/02/03/discoveries-at-the-edge-of-the-periodic-table-first-ever-measurements-of-einsteinium/
- National Cancer Institute Staff. (2020, October 26). Radiopharmaceuticals: Radiation therapy enters the molecular age. National Cancer Institute. https://www.cancer.gov/news-events/cancer-currents-blog/2020/radiopharmaceuticals-cancer-radiation-therapy
- Sathekge, M., Bruchertseifer, F., Knoesen, O., Reyneke, F., Lawal, I., Lengana, T., Davis, C., Mahapane, J., Corbett, C., Vorster, M., & Morgenstern, A. (2019). 225Ac-PSMA-617 in chemotherapy-naive patients with advanced prostate cancer: A pilot study. European Journal of Nuclear Medicine and Molecular Imaging, 46(1), 129–138. https://doi.org/10.1007/s00259-018-4167-0
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