Editing Astatine (section)

== Synthesis ==

=== Formation ===
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{| class="wikitable"
|+ Possible reactions after bombarding bismuth-209 with alpha particles
!rowspan=2| Reaction{{efn|A nuclide is commonly denoted by a symbol of the chemical element this nuclide belongs to, <!--if someone can come up with a better wording, please do, or, if you think it's okay, just remove this message--> preceded by a non-spaced superscript mass number and a subscript atomic number of the nuclide located directly under the mass number. (Neutrons may be considered as nuclei with the atomic mass of 1 and the atomic charge of 0, with the symbol being n.) With the atomic number omitted, it is also sometimes used as a designation of an isotope of an element in isotope-related chemistry.}}
!colspan=2| Energy of alpha particle
|-
! Threshold energy
! Maximum production
|-
| style="text-align:center;"| {{chem|209|83|Bi}} + {{chem|4|2|He}} → {{chem|211|85|At}} + 2 {{chem|1|0}}n
| style="text-align:center;"| 20.7&nbsp;MeV<ref name="Hermanne"/>
| style="text-align:center;"| 30<ref name="Gyehong"/>–31&nbsp;MeV<ref name="Hermanne"/>
|-
| style="text-align:center;"| {{chem|209|83|Bi}} + {{chem|4|2|He}} → {{chem|210|85|At}} + 3 {{chem|1|0}}n
| style="text-align:center;"| 28.4<ref name="zalutsky"/>–28.6&nbsp;MeV<ref name="Hermanne"/><ref name="Maiti"/>
| style="text-align:center;"| 37&nbsp;MeV<ref name="Hermanne">{{cite journal | last1=Hermanne | first1=A. | last2=Tárkányi | first2=F. | last3=Takács | first3=S. | last4=Szücs | first4=Z. | last5=Shubin | first5=Yu.N. | last6=Dityuk | first6=A.I. | title=Experimental study of the cross-sections of α-particle induced reactions on 209Bi | journal=Applied Radiation and Isotopes | publisher=Elsevier BV | volume=63 | issue=1 | year=2005 | issn=0969-8043 | doi=10.1016/j.apradiso.2005.01.015 | pages=1–9}}</ref>
|-
| style="text-align:center;"| {{chem|209|83|Bi}} + {{chem|4|2|He}} → {{chem|209|85|At}} + 4 {{chem|1|0}}n
| style="text-align:center;"| 35.9&nbsp;MeV<ref name="Maiti">{{cite journal | last1=Maiti | first1=Moumita | last2=Lahiri | first2=Susanta | last3=Kumar | first3=Deepak | last4=Choudhury | first4=Dibyasree | title=Separation of no-carrier-added astatine radionuclides from α-particle irradiated lead bismuth eutectic target: A classical method | journal=Applied Radiation and Isotopes | publisher=Elsevier BV | volume=127 | year=2017 | issn=0969-8043 | doi=10.1016/j.apradiso.2017.06.020 | pages=227–230| pmid=28649020 | bibcode=2017AppRI.127..227M }}</ref>
| style="text-align:center;"|
|}
</div>

[[File:Astatine-211 in bismuth target.jpg|thumb|left|The bismuth target after irradiation contains minuscule quantities of astatine-211.<ref>{{cite journal | last1=Naka | first1=Sadahiro | last2=Ooe | first2=Kazuhiro | last3=Shirakami | first3=Yoshifumi | last4=Kurimoto | first4=Kenta | last5=Sakai | first5=Toshihiro | last6=Takahashi | first6=Kazuhiro | last7=Toyoshima | first7=Atsushi | last8=Wang | first8=Yang | last9=Haba | first9=Hiromitsu | last10=Kato | first10=Hiroki | last11=Tomiyama | first11=Noriyuki | last12=Watabe | first12=Tadashi | title=Production of [211At]NaAt solution under GMP compliance for investigator-initiated clinical trial | journal=EJNMMI Radiopharmacy and Chemistry | volume=9 | issue=1 | date=2024-04-15 | issn=2365-421X | pmid=38619655 | pmc=11018728 | doi=10.1186/s41181-024-00257-z | doi-access=free}}</ref>]]

Astatine was first produced by bombarding bismuth-209 with energetic alpha particles, and this is still the major route used to create the relatively long-lived isotopes astatine-209 through astatine-211. Astatine is only produced in minuscule quantities, with modern techniques allowing production runs of up to 6.6&nbsp;[[gigabecquerel]]s<ref name="zalutsky"/> (about 86&nbsp;[[nanogram]]s or 2.47{{e|14}} atoms). Synthesis of greater quantities of astatine using this method is constrained by the limited availability of suitable cyclotrons and the prospect of melting the target.<ref name="zalutsky"/><ref name="Larsen" />{{efn|See however Nagatsu et al.<ref>{{cite journal |first1=K.|last1=Nagatsu|first2=K. H.|last2=Minegishi|first3=M. |last3=Fukada |first4=H. |last4=Suzuki |first5=S.|last5=Hasegawa |first6=M. |last6=Zhang|year=2014 |title=Production of <sup>211</sup>At by a vertical beam irradiation method|journal=Applied Radiation and Isotopes |volume=94 |pages=363–371 |doi=10.1016/j.apradiso.2014.09.012|pmid=25439168|bibcode=2014AppRI..94..363N }}</ref> who encapsulate the bismuth target in a thin aluminium foil and place it in a niobium holder capable of holding molten bismuth.}} Solvent [[radiolysis]] due to the cumulative effect of astatine decay<ref>{{cite book | title = Therapeutic Nuclear Medicine| year = 2014 | pages = 95–104 (99) | publisher = Springer | isbn = 978-3-540-36718-5 | last1 = Barbet | first1 = J. | last2 = Bourgeois | first2 = M.|first3= J.|last3= Chatal|editor1 = R. P.|editor2 = Baum|chapter= Cyclotron-Based Radiopharmaceuticals for Nuclear Medicine Therapy}}</ref> is a related problem. With cryogenic technology, [[microgram]] quantities of astatine might be able to be generated via proton irradiation of [[thorium]] or [[uranium]] to yield radon-211, in turn decaying to astatine-211. Contamination with astatine-210 is expected to be a drawback of this method.<ref name="Wilbur">{{cite journal | last = Wilbur| first = D. S. | date = 2001| title = Overcoming the Obstacles to Clinical Evaluation of <sup>211</sup>At-Labeled Radiopharmaceuticals | journal = The Journal of Nuclear Medicine | volume = 42 | issue = 10 | pages = 1516–1518 | url=http://jnm.snmjournals.org/content/42/10/1516|pmid=11585866}}</ref>

The most important isotope is astatine-211, the only one in commercial use. To produce the bismuth target, the metal is [[sputtering|sputtered]] onto a gold, copper, or aluminium surface at 50 to 100 milligrams per square centimeter. [[Bismuth oxide]] can be used instead; this is forcibly fused with a copper plate.{{sfn|Lavrukhina|Pozdnyakov|1970|p=233}} The target is kept under a [[Nitrogen gas#Reactions|chemically neutral nitrogen]] atmosphere,<ref name="BiN2">{{cite book|title=Inorganic Chemistry for Undergraduates|first=R. |last=Gopalan |year=2009|page=547|publisher=Universities Press | isbn = 978-81-7371-660-7 | url = https://books.google.com/books?id=Fs4zQ-hNTz8C&pg=PA492}}</ref> and is cooled with water to prevent premature astatine vaporization.{{sfn|Lavrukhina|Pozdnyakov|1970|p=233}} In a particle accelerator, such as a cyclotron,<ref>{{cite book|title=Targeted Radionuclide Tumor Therapy: Biological Aspects|first1=T.|last1=Stigbrand |first2=J. |last2=Carlsson |first3=G. P.|last3=Adams|year=2008|page=150|publisher=Springer | isbn = 978-1-4020-8695-3 | url = https://books.google.com/books?id=-mT0Lthq_54C}}</ref> alpha particles are collided with the bismuth. Even though only one bismuth isotope is used (bismuth-209), the reaction may occur in three possible ways, producing astatine-209, astatine-210, or astatine-211. Although higher energies can produce more astatine-211, it will produce unwanted astatine-210 that decays to toxic polonium-210 as well. Instead, the maximum energy of the particle accelerator is set to be below or slightly above the threshold of astatine-210 production, in order to maximize the production of astatine-211 while keeping the amount of astatine-210 at an acceptable level.<ref name="zalutsky"/><ref name="Gyehong">{{cite journal |first1=G.|last1=Gyehong |first2=K.|last2=Chun|first3=S. H. |last3=Park |first4=B.|last4=Kim|year=2014 |title=Production of α-particle emitting <sup>211</sup>At using 45&nbsp;MeV α-beam| journal=Physics in Medicine and Biology |volume=59 |issue=11|pages=2849–2860| doi=10.1088/0031-9155/59/11/2849|pmid=24819557 |bibcode = 2014PMB....59.2849K |s2cid=21973246 }}</ref>

=== Separation methods ===
Since astatine is the main product of the synthesis, after its formation it must only be separated from the target and any significant contaminants. Several methods are available, "but they generally follow one of two approaches—dry distillation or [wet] acid treatment of the target followed by solvent extraction." The methods summarized below are modern adaptations of older procedures, as reviewed by Kugler and Keller.{{sfn|Kugler|Keller|1985|pp=95–106, 133–139}}{{efn|See also Lavrukhina and Pozdnyakov.{{sfn|Lavrukhina|Pozdnyakov|1970|pp=243–253}}}} Pre-1985 techniques more often addressed the elimination of co-produced toxic polonium; this requirement is now mitigated by capping the energy of the cyclotron irradiation beam.<ref name="zalutsky"/>

==== Dry ====
The astatine-containing cyclotron target is heated to a temperature of around 650&nbsp;°C. The astatine [[Volatilization|volatilizes]] and is condensed in (typically) a [[cold trap]]. Higher temperatures of up to around 850&nbsp;°C may increase the yield, at the risk of bismuth contamination from concurrent volatilization. Redistilling the condensate may be required to minimize the presence of bismuth{{sfn|Kugler|Keller|1985|p=97}} (as bismuth can interfere with astatine [[radioactive tracer|labeling reactions]]). The astatine is recovered from the trap using one or more low concentration solvents such as [[sodium hydroxide]], [[methanol]] or [[chloroform]]. Astatine yields of up to around 80% may be achieved. Dry separation is the method most commonly used to produce a chemically useful form of astatine.<ref name="Larsen">{{cite journal|last1=Larsen|first1=R. H.|last2=Wieland|first2=B. W.|last3=Zalutsky|first3=M. R. J.|year=1996|title=Evaluation of an Internal Cyclotron Target for the Production of <sup>211</sup>At via the <sup>209</sup>Bi (α,2n)<sup>211</sup>At reaction|journal=Applied Radiation and Isotopes|volume=47|issue=2|pages=135–143|doi=10.1016/0969-8043(95)00285-5|pmid=8852627|bibcode=1996AppRI..47..135L }}</ref><ref>{{cite journal|last1=Lindegren|first1=S.|last2=Bäck|first2=T.|last3=Jensen|first3=H. J.|year=2001|title=Dry-distillation of Astatine-211 from Irradiated Bismuth Targets: A Time-saving Procedure with High Recovery Yields|journal=Applied Radiation and Isotopes|volume=55|issue=2|pages=157–160|doi=10.1016/S0969-8043(01)00044-6|pmid=11393754|bibcode=2001AppRI..55..157L }}</ref>

==== Wet ====
The irradiated bismuth (or sometimes [[bismuth trioxide]]) target is first dissolved in, for example, concentrated nitric or perchloric acid. Following this first step, the acid can be distilled away to leave behind a white residue that contains both bismuth and the desired astatine product. This residue is then dissolved in a concentrated acid, such as hydrochloric acid. Astatine is extracted from this acid using an organic solvent such as [[dibutyl ether]], [[diisopropyl ether]] (DIPE), or [[thiosemicarbazide]]. Using liquid-liquid extraction, the astatine product can be repeatedly washed with an acid, such as HCl, and extracted into the organic solvent layer. A separation yield of 93% using nitric acid has been reported, falling to 72% by the time purification procedures were completed (distillation of nitric acid, purging residual [[nitrogen oxide]]s, and redissolving [[bismuth nitrate]] to enable [[liquid–liquid extraction]]).<ref>{{cite journal|last1=Yordanov|first1=A. T.|last2=Pozzi|first2=O.|last3=Carlin|first3=S.|last4=Akabani|first4=G. J.|last5=Wieland|first5=B.|last6=Zalutsky|first6=M. R.|year=2005|title=Wet Harvesting of No-carrier-added <sup>211</sup>At from an Irradiated <sup>209</sup>Bi Target for Radiopharmaceutical Applications|url=https://link.springer.com/article/10.1007/s10967-004-0481-z|journal=Journal of Radioanalytical and Nuclear Chemistry|volume=262|issue=3|pages=593–599|doi=10.1007/s10967-005-0481-7|bibcode=2005JRNC..262..593Y |s2cid=93179195|url-access=subscription}}</ref><ref name="Balkin-2013">{{Cite journal|last1=Balkin|first1=Ethan|last2=Hamlin|first2=Donald|last3=Gagnon|first3=Katherine|last4=Chyan|first4=Ming-Kuan|last5=Pal|first5=Sujit|last6=Watanabe|first6=Shigeki|last7=Wilbur|first7=D.|date=2013-09-18|title=Evaluation of a Wet Chemistry Method for Isolation of Cyclotron Produced [211At]Astatine|journal=Applied Sciences|language=en|volume=3|issue=3|pages=636–655|doi=10.3390/app3030636|issn=2076-3417|citeseerx=10.1.1.383.1903|doi-access=free}}</ref> Wet methods involve "multiple radioactivity handling steps" and have not been considered well suited for isolating larger quantities of astatine. However, wet extraction methods are being examined for use in production of larger quantities of astatine-211, as it is thought that wet extraction methods can provide more consistency.<ref name="Balkin-2013" /> They can enable the production of astatine in a specific [[oxidation state]] and may have greater applicability in experimental [[radiochemistry]].<ref name="zalutsky"/>