Enigmatic Astatine D

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in your element Enigmatic astatine D. Scott Wilbur points out the difficulty in studying the transient element astatine, and the need to understand its basic chemical nature to help in the development of targeted radiotherapy agents.

ince the discovery of astatine The other ‘long’-lived isotope,210 At, is not of labelling reagents containing more over 70 years ago1, many of its suitable because it decays into polonium-210 stable aromatic astatine–boron bonds Scharacteristics have remained elusive. — the notorious radiation poison used to has improved that situation, and studies Unlike the other halogens, abundant and kill the Russian Federal Security Service evaluating bonding with other elements ubiquitous in nature, astatine is one of officer Alexander Litvinenko in 2006, may further advance it. the rarest of all elements. This arises from after he took political asylum in the To determine in vivo stability, the the fact that it has no stable isotopes; the United Kingdom. same cancer-targeting molecule can longest lived of its 32 known radioisotopes, Although some chemical data has be labelled with 211At and (stably) with 210At, has a half-life of only 8.1 hours. been compiled for astatine isotopes, radioiodine (125I, 123I or 131I), and the two The rarity and radioactive nature of many physical properties have only been co-injected. The concentrations of211 At element 85 lends to its mystery, as it cannot extrapolated. Similar to other halogens, in various tissues (higher lung, spleen, be observed or weighed in a conventional astatine undergoes nucleophilic and stomach and thyroid) indicate whether it is sense. Even its colour is unknown; based electrophilic reactions. The reproducibility being released from the carrier molecule. on increasingly dark colours for halogens of some reactions however has proved However, even in studies in which low from fluorine to iodine, however, black highly variable. This may arise in part from stomach and thyroid (neck) concentrations seems a logical guess. the low amounts of astatine suggest that 211At and 125I are both stable The rarity of this radioactive element present, resulting in very high to in vivo dehalogenation, very dissimilar is reflected in its name, derived from reaction dilutions. Quantities concentrations may be observed for the Greek word αστατοϚ (astatos) of 211At used in chemical and the two elements in other organs such meaning ‘unstable’ 2. What little radiolabelling reactions range as kidney and liver. This is likely to be astatine is present in nature comes from 37 kBq to 4 GBq. These due to variations in metabolism of the from the decay of heavy radioactive only represent from ~4.8 × 10–13 radioiodinated and astatinated molecules, elements found in the Earth’s to ~5.2 × 10–8 g of 211At — and this or may arise from preferential clearance of crust. The total amount of natural upper limit is rarely encountered, the radioiodinated metabolites. astatine at any given time has because of the costs involved and In the quest to produce targeted been estimated to be between the potential for radiation damage therapeutics for treatment of cancer and a few hundred milligrams3 and to the molecule being labelled. For other diseases, many of the basic chemical 30 g. In any case, naturally most reactions, the quantity of 211At studies with 211At have unfortunately been occurring astatine isotopes present ranges from 10–13–10–9 g, set aside. Although some of its physical are too unstable, and would and can be smaller than that of trace properties will continue to elude direct be too difficult to obtain, organic species and metals in solvents. characterization, it is apparent that we need for characterization. Impurities may thus interfere with to gain a better understanding of its basic Fortunately, the two the reactions studied, and might even chemical and radiochemical properties to longest-lived isotopes catalyse reaction pathways other than unravel the enigma of astatine. ❐ — 210At and 211At (half- that expected.

© DON HAMLIN life = 7.21 h) — can both The interest in211 At in medicine D. SCOTT WILBUR is at the Department be produced by α-beam irradiation mentioned above arises from its potential of Radiation Oncology, University of of bismuth-209 targets (pictured, on use in systemically targeted therapy of Washington, Box 355016, 616 NE Northlake aluminium support). cancers — it is one of only a few α-emitting Place, Seattle, Washington 98105, USA. Nevertheless, these longer-lived isotopes radioisotopes considered appropriate e-mail: [email protected] 4 5 can only be produced in small quantities , for medical use , as most others can References which, combined with their short half-lives cause severe damage to internal organs. 1. Corson, D. R. et al. Phys. Rev. 58, 672–678 (1940). and high costs, have considerably limited Its short path length (60–90 μm) and 2. Corson, D. R. et al. Nature 159, 24 (1947). astatine research. Of the artificial isotopes, high-energy α-particles (6.0–7.5 MeV) are 3. Kugler, H. K. & Keller, C. (eds) Astatine 10–14 (Gmelin, 211 Handbook of Inorganic Chemistry series, 1985). At has been the primary focus of chemical very effective in killing cells bound by a 4. Zalutsky M. R. & Pruszynski, M. Curr. Radiopharm. studies owing to its potential in medicine. carrier-targeting agent6. However, a major 4, 177–185 (2011). impediment to practical applications is the 5. Wilbur, D. S. Curr. Radiopharm. 4, 214–247 (2011). 6. Hall, R. J. & Giaccia A. J. Radiobiology for the Radiologist low stability of astatine bonds with aromatic 6th edn, 106–116 (Lipincott Williams & Wilkins, 2006). 7 carbon bonds in vivo . The development 7. Wilbur, D. S. Curr. Radiopharm. 1, 144–176 (2008). Pb Bi Po At Rn Fr Ra Ac Th Pa U Np Pu Am Cm Bk Cf Es Fm Md No 246 NATURE CHEMISTRY | VOL 5 | MARCH 2013 | www.nature.com/naturechemistry