Gallium-68 generator

A Gallium-68 generator , also called ⁶⁸ Ge / ⁶⁸ Ga generator, is a radionuclide generator for generating radioactive ⁶⁸Ga ³⁺ ions from the likewise radioactive ⁶⁸Ge . The ⁶⁸ Ga extracted from the generator is used in nuclear medicine to manufacture radiopharmaceuticals for positron emission tomography (PET).

Gallium-68

The naturally occurring element gallium consists of two non-radioactive isotopes : ⁶⁹ Ga, which makes up 60.1% of natural gallium, and ⁷¹ Ga, which makes up the remaining 39.9%. All others (i.e. the gallium isotopes that do not occur in nature) are radioactive. The isotope ⁶⁸ Ga decays with a half-life of only 67.629 minutes, 89% emitting a positron with a maximum of 1.9 MeV and 11% with electron capture ; in each case into the stable isotope ⁶⁸ Zn. The positron released - in 89% of decays - has a range of only a few millimeters in nuclear medicine, then it hits an electron and both elementary particles annihilate ( annihilate ) completely to form two photons each 511 keV ( gamma radiation ). The two photons are emitted from the place of destruction at an angle of almost 180 ° from each other. The emitted photons can be detected with appropriate detectors and the location of the annihilation can be determined very precisely by reconstructing several detection events. See the main article: Positron Emission Tomography

With its physical and chemical properties, ⁶⁸ Ga is ideally suited for nuclear medicine examinations. The short half-life fits very well with the pharmacokinetics of many peptides , to which it is usually bound in diagnostics with the strong chelator DOTA . The complexation of the gallium ions with DOTA is relatively simple and quick. On the other hand, the short half-life of 68 minutes makes shipping or even storing this isotope almost impossible. However, this dilemma is solved with the ⁶⁸ Ge / ⁶⁸ Ga generator.

Principle of the gallium 68 generator

In the ⁶⁸ Ge / ⁶⁸ Ga generator, the required radionuclide ⁶⁸ Ga is generated from the likewise radioactive ⁶⁸ Ge. This isotope has a half-life of 270.8 days and breaks down into the shorter-lived ⁶⁸ Ga with electron capture . In the generator, the germanium is bound to an insoluble matrix of an inert carrier (usually titanium (IV) oxide ). In the generator itself, due to the continuous decay of the germanium, ⁶⁸ Ga is constantly being formed, which, however, cannot accumulate in large quantities due to its much faster decay. A largely constant concentration of generated (generated) ⁶⁸ Ga ( ⁶⁸ Ge / ⁶⁸ Ga equilibrium) is therefore formed in the generator . This amount of ⁶⁸ Ga decreases by two events:

by eluting ("milking") the generator with the help of a solvent in which only ⁶⁸ Ga is soluble, but not ⁶⁸ Ge (e.g. hydrochloric acid)
the slow decrease in the ⁶⁸ Ge content caused by its own decay.

In the first case, the radioactive equilibrium between ⁶⁸ Ge / ⁶⁸ Ga builds up again after each elution . After a half-life, i.e. 68 minutes, half of the original concentration has already been reached. Usually, a waiting time of four to five hours is sufficient before the next removal. The slow decay of ⁶⁸ Ge causes the amount of ⁶⁸ Ga formed in the generator to continuously decrease, by exactly half after 270.8 days. The service life of a ⁶⁸ Ge / ⁶⁸ Ga generator used in practice is about one year.

application

The in ⁶⁸ Ge / ⁶⁸ Ga generator produced ⁶⁸ Ga is used for a number of diagnostic tests using positron emission tomography. Most of these methods are, however, still in clinical testing. The most common is the occupancy of Edotreotide (DOTATOC) with ⁶⁸ Ga to ⁶⁸ Ga-DOTATOC.

Manufacturing

The ⁶⁸ Ge used in ⁶⁸ Ga generators is produced by irradiating the stable isotope ⁶⁹ Ga with accelerated protons (p, 2n).

{\ displaystyle \ mathrm {{} _ {31} ^ {69} Ga \ + \ {} _ {1} ^ {1} p \ longrightarrow {} _ {32} ^ {68} Ge \ + \ 2 \ { } _ {0} ^ {1} n}}

Some of the generators are produced in Obninsk ( Russia ).

perspective

In general, the ⁶⁸ Ge / ⁶⁸ Ga generator is predicted to have great future potential in clinical use. So far, however, its use has been limited to larger nuclear medicine centers. The great advantage over the other isotopes commonly used in PET, such as ¹⁸ F, is that there is no need for complex and expensive cyclotrons in the immediate vicinity.

Individual evidence

↑ ^a ^b I. Velikyan: Synthesis, Characterization and Application of ⁶⁸ Ga-labeled Macromolecules. Dissertation, Uppsala University, 2005.
↑ RM Lambrecht, M. Sajjad: Accelerator-derived radionuclide generators. In: Radiochim. Acta 43/1988, pp. 171-179.
↑ HR Maecke, JP André: 68Ga-PET radio pharmacy: A generator-based alternative to 18F-radio pharmacy. In: Ernst Schering Res Found Workshop 62/2007, pp. 215–242. PMID 17172157
↑ WA Breeman, AM Verbruggen: The 68Ge / 68Ga generator has high potential, but when can we use 68Ga-labeled tracers in clinical routine? In: Eur J Nucl Med Mol Imaging 34/2007, pp. 978-981. PMID 17333177

literature

M. Nakayama et al .: A new 68Ge / 68Ga generator system using an organic polymer containing N-methylglucamine groups as adsorbent for 68Ge. In: Appl Radiat Isot 58/2003 , pp. 9-14. PMID 12485657
KP Zhernosekov et al: Processing of generator-produced 68Ga for medical application. In: J Nucl Med 48/2007, pp. 1741-8. PMID 17873136
J. Lösch: Attack of the positron emitters (PDF; 878 kB) In: Insight 4/2003, pp. 2–5.
S. Koukouraki: Comparison of the pharmacokinetics of 68Ga-DOTATOC and [18F] FDG in patients with metastatic neuroendocrine tumors scheduled for 90Y-DOTATOC therapy. In: Eur J Nucl Med Mol Imaging 33/2006, pp. 1115-22. PMID 16763820
RC Barrall: Purity tests of a 68Ge-68Ga generator. In: Int J Appl Radiat Isot 22/1971, pp. 149-54. PMID 5574803
M. Yamashita: A trial using tin (IV) oxide for reduction of 68Ge contamination in eluates from an ionic 68Ga generator. In: Radioisotopes 35/1986, pp. 133-135. PMID 3715067
M. Gabriel et al .: Ga68-DOTA-Tyr3-Octreotide PET in Neuroendocrine Tumors: Comparison with Somatostatin Receptor Scintigraphy and CT. In: J Nucl Med 2007 Apr; 48 (4) pp. 508-518 PMID 17401086
C. Decristoforo at al .: A fully automated synthesis for the preparation of Ga68-labeled peptides. In: Nuclear Medicine Communications 2007 Nov; 28 (11) pp. 870-5 PMID 17901771

Web links

Wikibooks: Physical basics of nuclear medicine / production of radionuclides - learning and teaching materials

[irina-1] I. Velikyan: Synthesis, Characterization and Application of ⁶⁸ Ga-labeled Macromolecules. Dissertation, Uppsala University, 2005.

[2] RM Lambrecht, M. Sajjad: Accelerator-derived radionuclide generators. In: Radiochim. Acta 43/1988, pp. 171-179.

[3] HR Maecke, JP André: 68Ga-PET radio pharmacy: A generator-based alternative to 18F-radio pharmacy. In: Ernst Schering Res Found Workshop 62/2007, pp. 215–242. PMID 17172157

[4] WA Breeman, AM Verbruggen: The 68Ge / 68Ga generator has high potential, but when can we use 68Ga-labeled tracers in clinical routine? In: Eur J Nucl Med Mol Imaging 34/2007, pp. 978-981. PMID 17333177