**5. Gallium-68: a brief profile**

Gallium is located in group 13 in the 4th period. It has 31 known isotopes and 11 metastable isomers including the two natural occurring stable isotopes gallium-69 (60.11%) and gallium-71 (39.89%). Two gallium isotopes are applied in nuclear medicine for PET-imaging: gallium-67, which has the longest half-life (T1/2 = 3.26 d) of the instable 68Ga-isotopes, and gallium-68 (T1/2 = 67.71 min).

**27**

*Gallium-68: Radiolabeling of Radiopharmaceuticals for PET Imaging - A Lot to Consider*

**Positron emitter Half-life ~**

Ga(III) is a hard Lewis acid forming complexes coordinating four, five or six ligands. The most stable complexes are the last-mentioned with a octahedral coordination sphere in which oxygen, nitrogen and sulfur donor atoms form coordination bonds with Ga(III). To ensure the complex formation thorough pH, control is required to ensure deprotonation of the electron donor and to protect Ga(III) from

Gallium-68 67.71 min 0.829 1.899 Flourine-18 109.77 min 0.250 0.634

*Eβ) and maximum (Eβ, max) positron energies of gallium-68 and fluorine-18 [24].*

*E***<sup>β</sup> Eβ, max**

**[MeV]**

Gallium-68 is a positron emitter that decays with a half-life of 67.71 min and 89% positron branching to stable zinc-68. The transition is accompanied by lowabundant photon emission (1077 keV, 3.22%) [23]. **Table 1** shows the mean and maximum energies of the positrons emitted in comparison to fluorine-18.

One of the reasons of the emerging application of gallium-68 in nuclear medicine is its cyclotron-independency and availability via radionuclide generator. Since the application of gallium-68 was a long time limited to research, advancements in generator design facilitated research on new 68Ga-radiopharmaceuticals as well as

Physical basis for radionuclide generators is the existence of the radioactive equilibria. The differentiation between radionuclide generations is based on the half-lives of the parent (1) and its daughter (2). Depending on the ratio between the

1.Transient equilibrium. Longer living parent but not more than factor 100:

The basis for the 68Ge/68Ga-generator is the secular equilibrium between the parent radionuclide germanium-68 and its daughter gallium-68. Germanium-68 decays with T1/2 = 270.95 days via electron capture to gallium-68. This transition is subsequently followed by decay of gallium-68 to stable zinc-68. At equilibrium, the quantity of gallium-68 produced is equal to the quantity of gallium-68 decaying, while the parent activity does not significantly decrease over many half-lives of the daughter. The theoretical maximum activity or equilibrium state for a certain

> λ<sup>2</sup> − λ<sup>1</sup> *ln* \_ λ2 λ1

(1)

2.Secular equilibrium. Much longer living parent: T1/2, 2 < < T1/2,1.

*DOI: http://dx.doi.org/10.5772/intechopen.90615*

**Table 1.**

*Comparison of mean (<sup>~</sup>*

forming Ga(OH)3 precipitating at pH 3–7 [22].

**6. Availability: sources of gallium-68**

two half-lives, three principal cases can be distinguished:

generator system can be obtained at the time t (**Figure 3**):

*<sup>t</sup>* <sup>=</sup> \_1

3.No equilibrium. Shorter living parent.

**6.1 Traditional: 68Ge/68Ga-generator**

clinical use of the known.

T1/2, 2 < T1/2,1 < 100.

*Gallium-68: Radiolabeling of Radiopharmaceuticals for PET Imaging - A Lot to Consider DOI: http://dx.doi.org/10.5772/intechopen.90615*


#### **Table 1.**

*Medical Isotopes*

prostate cancer imagine.

carcinoembryonic antigen (CEA) [20].

**4. Radiometals: special needs?**

following is recommended by the IAEA [21]:

• Consider coating of your fume hood.

**5. Gallium-68: a brief profile**

• Use plastic disposables/contact materials

reagents (e.g. pipettes, spatulas, vials, etc.)

[

cancers, renal cell cancer and gastrointestinal stromal tumors. An amphibian homolog of the mammalian gastrin-releasing peptide bombesin was intensively investigated, also radiolabelled with gallium-68, for imaging of GRPR. For integrin αvβ3, specific imaging probes usually use the peptide arginine-glycine-aspartic acid (RGD). For imagine of GRPR, several radiopharmaceuticals based on gallium-68 were proposed, in particular [68Ga]Ga-BBN-RGD for breast cancer imagine [17],

68Ga]Ga-NOTA-Aca-BBN for glioma imagine [18], [68Ga]-NOTA-DUPA-RM26 for

Another promising area of application of 68Ga-based radiopharmaceuticals is the labeling of human epidermal growth factor receptor family (HER2) [19] and

Even though gallium-68 is a very convenient radionuclide for use in radiopharmacy, it is widespread in radiopharmaceuticals in comparison with other diagnostic isotopes. But usability and the commercially availability of generator simplified research and motivated developments with a view to a broad routine application.

Radiolabeling with radiometals is in some ways challenging. Due to the very low amount of substance, other metals present in the reaction mixture can be serious problem and noticeably effect the radiolabeling. These metallic impurities can compete with gallium-68 for the chelating function of the precursor and are compared with gallium-68 (1 GBq equals to 9.73×10<sup>−</sup>12 mol) even when present at low levels (<ppm) clearly in excess number. They are result of external influences (e.g. production of starting materials) or are an intrinsic generator property (e.g. matrix; decay product). To avoid additional or larger impurities than necessary, the

• Avoid contact with metals of your working equipment during preparation of

• Protect your working materials from direct contact with metals (e.g. surfaces,

• Use chemicals and water with lowest metal content as possible (e.g. ultra-pure

Gallium is located in group 13 in the 4th period. It has 31 known isotopes and 11 metastable isomers including the two natural occurring stable isotopes gallium-69 (60.11%) and gallium-71 (39.89%). Two gallium isotopes are applied in nuclear medicine for PET-imaging: gallium-67, which has the longest half-life (T1/2 = 3.26 d)

• Do not use standard laboratory glassware (e.g. beakers, etc.)

of the instable 68Ga-isotopes, and gallium-68 (T1/2 = 67.71 min).

**26**

etc.)

grade)

*Comparison of mean (<sup>~</sup> Eβ) and maximum (Eβ, max) positron energies of gallium-68 and fluorine-18 [24].*

Ga(III) is a hard Lewis acid forming complexes coordinating four, five or six ligands. The most stable complexes are the last-mentioned with a octahedral coordination sphere in which oxygen, nitrogen and sulfur donor atoms form coordination bonds with Ga(III). To ensure the complex formation thorough pH, control is required to ensure deprotonation of the electron donor and to protect Ga(III) from forming Ga(OH)3 precipitating at pH 3–7 [22].

Gallium-68 is a positron emitter that decays with a half-life of 67.71 min and 89% positron branching to stable zinc-68. The transition is accompanied by lowabundant photon emission (1077 keV, 3.22%) [23]. **Table 1** shows the mean and maximum energies of the positrons emitted in comparison to fluorine-18.
