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A germanium-68/gallium-68 generator is a device used to extract the positron-emitting isotope 68Ga of
gallium Gallium is a chemical element with the symbol Ga and atomic number 31. Discovered by French chemist Paul-Émile Lecoq de Boisbaudran in 1875, Gallium is in group 13 of the periodic table and is similar to the other metals of the group ( alum ...
from a source of decaying germanium-68. The parent isotope 68Ge has a
half-life Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable at ...
of 271 days and can be easily utilized for in-hospital production of generator produced 68Ga. Its decay product gallium-68 (with a half-life of only 68 minutes, inconvenient for transport) is extracted and used for certain
positron emission tomography Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, ...
nuclear medicine Nuclear medicine or nucleology is a medical specialty involving the application of radioactive substances in the diagnosis and treatment of disease. Nuclear imaging, in a sense, is "radiology done inside out" because it records radiation emit ...
diagnostic procedures, where the radioisotope's relatively short half-life and emission of positrons for creation of 3-dimensional
PET scan Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, r ...
s, are useful.


Parent isotope (68Ge) source

The parent isotope germanium-68 is the longest-lived (271 days) of the radioisotopes of germanium. It has been produced by several methods. In the U.S., it is primarily produced in proton accelerators: At
Los Alamos National Laboratory Los Alamos National Laboratory (often shortened as Los Alamos and LANL) is one of the sixteen research and development laboratories of the United States Department of Energy (DOE), located a short distance northwest of Santa Fe, New Mexico, i ...
, it may be separated out as a product of
proton capture Proton capture is a nuclear reaction in which an atomic nucleus and one or more protons collide and merge to form a heavier nucleus. Since protons have positive electric charge, they are repelled electrostatically by the positively charged nuc ...
, after proton irradiation of Nb-encapsulated gallium metal. At
Brookhaven National Laboratories Brookhaven National Laboratory (BNL) is a United States Department of Energy national laboratory located in Upton, Long Island, and was formally established in 1947 at the site of Camp Upton, a former U.S. Army base and Japanese internment ca ...
, 40 MeV proton irradiation of a gallium metal target produces germanium-68 by
proton capture Proton capture is a nuclear reaction in which an atomic nucleus and one or more protons collide and merge to form a heavier nucleus. Since protons have positive electric charge, they are repelled electrostatically by the positively charged nuc ...
and double neutron
knockout A knockout (abbreviated to KO or K.O.) is a fight-ending, winning criterion in several full-contact combat sports, such as boxing, kickboxing, muay thai, mixed martial arts, karate, some forms of taekwondo and other sports involving striking, a ...
, from gallium-69 (the most common of two stable isotopes of gallium). This reaction is: 69Ga(p,2n)68Ge. 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 generator A technetium-99m generator, or colloquially a technetium cow or moly cow, is a device used to extract the metastable isotope 99mTc of technetium from a decaying sample of molybdenum-99. 99Mo has a half-life of 66 hours and can be easily transp ...
s, in both cases using a process similar to
ion chromatography Ion chromatography (or ion-exchange chromatography) separates ions and polar molecules based on their affinity to the ion exchanger. It works on almost any kind of charged molecule—including large proteins, small nucleotides, and amino ac ...
. 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 Electron capture (K-electron capture, also K-capture, or L-electron capture, L-capture) is a process in which the proton-rich nucleus of an electrically neutral atom absorbs an inner atomic electron, usually from the K or L electron shells. T ...
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 Hydrochloric acid, also known as muriatic acid, is an aqueous solution of hydrogen chloride. It is a colorless solution with a distinctive pungent smell. It is classified as a strong acid. It is a component of the gastric acid in the dig ...
from generators using metal-free
tin dioxide Tin(IV) oxide, also known as stannic oxide, is the inorganic compound with the formula SnO2. The mineral form of SnO2 is called cassiterite, and this is the main ore of tin. With many other names, this oxide of tin is an important material in ...
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 Edotreotide ( USAN, also known as (DOTA0- Phe1- Tyr3) octreotide, DOTA-TOC, DOTATOC) is a substance which, when bound to various radionuclides, is used in the treatment and diagnosis of certain types of cancer. When used therapeutically it is an ...
or
DOTA-TATE DOTA-TATE (DOTATATE, DOTA-octreotate, oxodotreotide, DOTA-(Tyr3)-octreotate, and DOTA-0-Tyr3-Octreotate) is an eight amino acid long peptide, with a covalently bonded DOTA bifunctional chelator. DOTA-TATE can be reacted with the radionuclides ...
, 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 Edotreotide (USAN, also known as (DOTA0- Phe1- Tyr3) octreotide, DOTA-TOC, DOTATOC) is a substance which, when bound to various radionuclides, is used in the treatment and diagnosis of certain types of cancer. When used therapeutically it is an e ...
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.


Indications for gallium-68 PET scanning

Gallium-67 citrate salt imaging is useful for imaging old or sterile abscesses. Gallium-68 is useful in direct
tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
imaging, especially
leukocyte White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mul ...
-derived
malignancies Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...
and prostate cancer
metastases Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, the ...
.


See also

* Isotopes of germanium *
Positron emission tomography Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, ...
*
Technetium-99m generator A technetium-99m generator, or colloquially a technetium cow or moly cow, is a device used to extract the metastable isotope 99mTc of technetium from a decaying sample of molybdenum-99. 99Mo has a half-life of 66 hours and can be easily transp ...


References

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External links



M.D. Anderson article on automated synthesis of tracer molecules from gallium-68 in as little as 20 minutes, for PET scan uses. Radiopharmaceuticals Radioactivity Gallium Medical physics