Active Actinium Naturally Scarce but Synthetically Accessible, Gauthier J.-P

in your element Active actinium Naturally scarce but synthetically accessible, Gauthier J.-P. Deblonde and Rebecca J. Abergel discuss element 89 and its emergence as a candidate radio-theranostic metal for cancer treatment. n 1899, during the aftermath of applications, the day-scale decay of the now Marie and Pierre Curie’s resounding easily accessible 225Ac makes it a seemingly Idiscovery of both polonium and radium, ideal candidate for destroying tumour cells. André-Louis Debierne — one of their Its final decay to the stable and non-toxic French research fellows — partially isolated 209Bi is also beneficial when compared with another new element. Ambiguities in competitors under clinical evaluation, namely Debierne’s purification procedure from 227Th,228 Th and 230U, all of which alpha-decay pitchblende residues almost cost him the to stable, but toxic, Pb isotopes. credit for the discovery of element 89, A rising challenge for chemists resides with Friedrich Oskar Giesel independently in the handling of 225Ac intermediates and managing to isolate the same isotope just potentially harmful recoiling daughters — three years later. After some discussion, 221Fr, 217At, and 213Po. The design of in vivo Debierne’s actinium (for the Greek aktinos, stable carriers able to scavenge both actinium meaning ray) was preferred to Giesel’s and its alpha cascade raises hope for highly emanium; although both names highlight its efficient cancer therapies with no side effects. active alpha-particle emanations. Various strategies are under development, The discovery of Ac was a continuation of among which the encapsulation within the work of the Curies, but never had the same nanoparticles seems most promising, impact as its freshly discovered radioactive whereby tumour delivery of 225Ac through a neighbour, Ra. Indeed contrary to radium- OF ENERGY US DEPT. LABORATORY, RIDGE NATIONAL OF OAK COURTESY lanthanide-based ‘nanosafe’ could neutralize based therapies, actinium had no commercial Purified 225Ac emitting Cerenkov luminescence. metastases without leaving radioactive applications at the time, and its extreme rarity traces in the patient4. Finally, Cerenkov in nature made it almost impossible to extract luminescence imaging of targeted tissues from ores — a process that is still difficult even through neutron or proton irradiation of using the in situ decay of 225Ac and its with today’s technologies. 226Ra or 232Th targets. daughter products has recently brought to Unlike 226Ra, which has a relatively Beyond credit for discovery, the debate light the formidable theranostic potential of 225 5 long half-life (t1/2) of 1,600 years, the only on the position of actinium in the periodic Ac-based radiopharmaceuticals . naturally occurring isotopes of actinium are table is still highly active2. Although the name The quest for an efficient and silent, but 227 Ac (t1/2 = 21.8 years), which comes from actinium would unambiguously make it the traceable cancer treatment could turn into the decay of the already rare 235U, and 228Ac first member of the actinide family, Ac is still reality thanks to an element that has been (t1/2 = 6.1 hours), a furtive decay product of placed below Sc, Y and La in most periodic largely overlooked since its discovery. Studies 232Th. The elusive nature of Ac, combined tables. Recent arguments tend to support its of actinium have taken researchers through with two world wars in the first half of the reassignment as an actual f-block member the realms of radiochemistry, nuclear science, twentieth century, resulted in the knowledge with irregular electronic configuration, particle physics, medicine, and more recently of no new isotopes until 1947, though 32 have whereas the current heaviest actinide, Lr, nanomaterial design, underlining how now been identified and 60 more are expected would be drafted to the d-block below Sc, Y Ac chemistry is as highly active as ever. ❐ to exist. Unfortunately, this profusion of new and Lu. Regardless of whether Ac is an f- or man-made Ac isotopes synthesized since d-element, its chemistry has experienced a GAUTHIER J.-P. DEBLONDE and the 1950’s has not produced any long-lived revival in the past few years3. Indeed, actinium REBECCA J. ABERGEL are in the Chemical actinium atoms, they all actively decay in a may supersede radium due to its ongoing Sciences Division, Lawrence Berkeley National few hours at best, with the exception of 225Ac development in alpha-emitting radionuclide Laboratory, MS 70A-1150, One Cyclotron (t1/2 = 10 days). Bulk chemical studies on therapies. If chelated and targeted adequately, Road, Berkeley, California 94720, USA. actinium are therefore still dependent on the the tremendous energy released by the e-mail: [email protected]; [email protected] original 227Ac (ref. 1). Nonetheless, progress fourfold alpha disintegrations of 225Ac could References in particle accelerators and nuclear reactions be used to surgically strike prostate, breast 1. Ferrier, M. G. et al. Nat. Commun. 7, 12312 (2016). 227 225 made both Ac and Ac more accessible and bone marrow cancer tumours. In contrast 2. Castelvecchi, D. Nature http://doi.org/bq8s (2015). to very short-lived isotopes such as 213Bi 3. Miederer, M., Scheinberg, D. A. & McDevitt, M. R. Adv. Drug 211 Deliv. Rev. 60, 1371–1382 (2008). (t1/2 = 46 minutes) and At (t1/2 = 7.2 hours) 4. McLaughlin, M. F. et al. PLOS One 8, e54531 (2013). that have been evaluated for these 5. Pandya, D. N. et al. Theranostics 6, 698–709 (2016). Rn Fr Ra Ac Th Pa U Np Pu Am Cm Bk Cf Es Fm Md No Lr Rf Db Sg 1084 NATURE CHEMISTRY | VOL 8 | NOVEMBER 2016 | www.nature.com/naturechemistry ©2016 Mac millan Publishers Li mited, part of Spri nger Nature. All ri ghts reserved. .

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