Gallium-68 generator

{{Short description|Device to extract gallium-68 from germanium-68}} A '''germanium-68/gallium-68 generator''' is a device used to extract the positron-emitting isotope ⁶⁸Ga of gallium from a source of decaying germanium-68. The parent isotope ⁶⁸Ge has a half-life of 271.05 days and can be easily utilized for in-hospital production of ⁶⁸Ga. Its decay product gallium-68 (half-life 67.84 minutes, inconvenient for transport) is extracted and used for certain positron emission tomography nuclear medicine diagnostic procedures, where the radioisotope's relatively short half-life and emission of positrons are useful for creation of 3-dimensional PET scans.

==Parent isotope (⁶⁸Ge) source == The parent isotope germanium-68 is the longest-lived of the radioisotopes of germanium. It has been produced by several methods.<ref>{{Cite web |url=http://www.med.harvard.edu/JPNM/physics/isotopes/Ge/Ge68/prod.html |title=Note on Ge-68 production methods in 1996. Accessed March 15, 2010 |access-date=March 15, 2010 |archive-date=June 11, 2011 |archive-url=https://web.archive.org/web/20110611043400/http://www.med.harvard.edu/JPNM/physics/isotopes/Ge/Ge68/prod.html |url-status=dead }}</ref> In the U.S., it is primarily produced in proton accelerators: the reaction is ⁶⁹Ga(p,2n)⁶⁸Ge (the target is the more abundant consituent of natural gallium). At Los Alamos National Laboratory, it may be separated out after proton irradiation of Nb-encapsulated gallium metal.<ref>{{cite journal|last1=Bach|first1=H. T.|last2=Claytor|first2=T. N.|last3=Hunter|first3=J. F.|last4=Olivas|first4=E. R.|last5=Kelsey|first5=C. T.|last6=Connors|first6=M. A.|last7=Nortier|first7=F. M.|last8=Runde|first8=W. H.|last9=Modrell|first9=C.|last10=Lenz|first10=J. W.|last11=John|first11=K. D.|title=Improving the survivability of Nb-encapsulated Ga targets for the production of Ge-68|journal=Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms|date=15 March 2013|volume=299|pages=32–41|doi=10.1016/j.nimb.2013.01.035}}</ref> It is also produced at Brookhaven National Laboratories by 40 MeV proton irradiation of a gallium metal target.

A Russian source produces germanium-68 from accelerator-produced helium ion (alpha) irradiation of zinc-66, again after knockout of two neutrons, in the nuclear reaction ⁶⁶Zn(α,2n)⁶⁸Ge.

== Mechanism of generator function == When loaded with the parent isotope germanium-68, these generators function similarly to technetium-99m generators, in both cases using a process similar to ion chromatography. The stationary phase is either metal-free or alumina, TiO₂ or SnO₂, onto which germanium-68 is adsorbed. The use of metal-free columns allows direct labeling of ⁶⁸Ga without prepurification, hence making production of gallium-68-radiolabeled compounds more convenient. The mobile phase is a solvent able to elute (wash out) gallium-68 (III) (⁶⁸Ga³⁺) after it has been produced by electron capture decay from the immobilized (absorbed) germanium-68.

Currently, such ⁶⁸Ga (III) is easily eluted with a few mL of 0.05 M, 0.1 M or 1.0 M hydrochloric acid from generators using metal-free tin dioxide<ref>{{cite journal | last1 = Loc'h | first1 = C | last2 = Mazièré | first2 = B | last3 = Comar | first3 = D | title = A new generator for ionic gallium-68 | journal = Journal of Nuclear Medicine | volume = 21 | issue = 2 | pages = 171–3 | year = 1980 | pmid = 6965408 |name-list-style=vanc }}</ref> or titanium dioxide adsorbents, respectively, within 1 to 2 minutes. With generators of tin dioxide and titanium dioxide-based adsorbents, there once remained more than an hour of pharmaceutical preparation to attach the gallium-68 (III) as a tracer to the pharmaceutical molecules DOTATOC or DOTA-TATE, so that the total preparation time for the resulting radiopharmaceutical is typically longer than the ⁶⁸Ga isotope half-life. This fact required that these radiopharmaceuticals be made on-site in most cases, and the on-site generator is required to minimize the time losses. However, new kits such as "NETSPOT" for more rapidly preparing Ga-68 edotreotide or DOTATATE from Ga-68(III) ions have increased the flexibility of sourcing of this radiopharmaceutical for Ga-68 endocrine receptor (octreotide) scans. With NETSPOT the preparation of the Ga-68 DOTATATE is immediate once the Ga-68 has been acquired from the generator and mixed with the reagent. <ref>{{Cite web|url=https://www.dmshealth.com/the-clinical-impact-of-utilizing-netspot/|title=The Clinical Impact of Utilizing NETSPOT - DMS Health|date=19 September 2019}}</ref>

==Indications for gallium-68 use== {{main|Gallium scan}} Gallium-67 is useful for imaging old or sterile abscesses. Gallium-68 is useful in direct tumor imaging, especially leukocyte-derived malignancies and prostate cancer metastases.

== See also == *Isotopes of germanium *Positron emission tomography *Technetium-99m generator

== References == {{reflist}}

==External links== *[https://web.archive.org/web/20110720032833/http://www2.mdanderson.org/app/techcommerc/body.cfm?mdaref=MDA04-016] M.D. Anderson article on automated synthesis of tracer molecules from gallium-68 in as little as 20 minutes, for PET scan uses.

Category:Radiopharmaceuticals Category:Radioactivity Category:Gallium Category:Medical physics