Gallium is used in both diagnostic and therapeutic areas of human medicine.
Isotopes ⁶⁷Ga and ⁷²Ga are used as radioactive markers in the diagnosis of certain cancers, such as lymphomas, because of gallium’s predisposition to accumulate more at sites of active proliferation.

68Ga with a half-life of only 68 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 for creation of 3-dimensional PET scans, are useful. ⁶⁸Ga can be produced with a cyclotron (solid or liquid target) or a generator.
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 days and can be easily utilized for in-hospital production of generator produced 68Ga.

germanium-68/gallium-68 generator functioning: 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 pre-purification, 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 or titanium dioxide adsorbents, espectively, 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; unless there is the possibility to produce big amount of ⁶⁸Ga, for example with a solid target. In this case with a production of 1Ci or more of ⁶⁸Ga).

In case of ⁶⁸Ga production with a ⁶⁸Ge generator, to avoid exposures to the operators
Comecer proposes this hot cell:

Another hot cell can be:

⁶⁸Ga can also be produced directly on the cyclotron via the ⁶⁸Zn(p,n)⁶⁸Ga nuclear reaction, with various production routes. Depending on the production technique, cyclotron ⁶⁸Ga yields are typically one to several orders of magnitude greater than currently available ⁶⁸Ga/⁶⁸Ge generators. Significant development has been undertaken in the field of liquid targets for ⁶⁸Ga production. Aqueous solutions of isotopically enriched zinc-68 (⁶⁸Zn) zinc nitrate in nitric acid were subjected to proton bombardment producing 9.85 ± 2.09 GBq at EOB.

Alternatively, solid targets using electroplated or pressed metal ⁶⁸Zn powder have been used, where ⁶⁸Zn is electroplated or pressed onto metallic target backings. Post-irradiation, the metallic ⁶⁸Zn is dissolved for chemical separation and ⁶⁸Ga purification. An alternative target system combining irradiation and dissolution has recently been developed that aims to address the limitations of solid and liquid targetry.

Liquid ⁶⁸Zn target solutions are prepared by dissolving isotopically enriched ⁶⁸Zn metal or ⁶⁸Zn oxide in nitric acid to produce [⁶⁸Zn]Zn(NO₃)₂ . It was found that irradiating ZnCl₂ leads to a significant pressure buildup of hydrogen and oxygen resulting from beam-induced radiolysis of the target solution. Target assemblies can utilize a combination of helium and water cooling to remove heat, with the target solution and cooling fluids separated by aluminum and niobium foils. Targets are typically irradiated at energies of 12–14 MeV up to 45 µA beam current with ⁶⁸Ga yields dependent on the target pressure and concentration of ⁶⁸Zn solution, yielding up to 9.85 GBq after a 60 min irradiation. While irradiating at higher beam energies increases 68Ga yield, it increases production of the ⁶⁷Ga radionuclidic impurity, so irradiating at a lower energy of ~ 12 MeV improves radionuclidic purity through avoiding onset of the ⁶⁸Zn(p,2n)⁶⁷Ga reaction. However trace levels of undesired isotopic impurities (0.1% ⁶⁶Zn and 0.48% ⁶⁷Zn) present in highly enriched ⁶⁸Zn (99.3%) lead to unavoidable production of ⁶⁶Ga and ⁶⁷Ga from the ⁶⁶Zn(p,n)⁶⁶Ga and ⁶⁷Zn(p,n)⁶⁷Ga reactions, respectively. 

Solid ⁶⁸Zn targets are prepared by either by electroplating or pressing ⁶⁸Zn powder and irradiating at the same beam energies as liquid targets to achieve similar radioisotopic purity. Electroplated targets are produced using platinum, gold, or silver target backings, with the desired cyclotron beam-spot on the target backing immersed in a [⁶⁸Zn]ZnCl₂ electroplating solution to deposit 40–250 mg ⁶⁸Zn metal on a 7–12 mm target beam-spot. 
Targets are then irradiated at currents up to 35 μA beam current at from 12 to 14.5 MeV , yielding up to 60.9 GBq after a 60 min irradiation. Similar to liquid targets, solid targets use helium and water cooling, with helium cooling provided across the front of the target assembly, while water cooling flows along the target backside. It is important to achieve an even cyclotron beam distribution across the ⁶⁸Zn target material to avoid excessive heat loads concentrated on small areas of the target. For both electroplating and pressed powder targetry, an optimal ⁶⁸Zn pellet thickness can be selected based upon production requirements, with thicker ⁶⁸Zn targets yielding greater ⁶⁸Ga for a given irradiation time at the cost of a greater material expense. Advantages of ⁶⁸Zn solid targetry include much greater ⁶⁸Ga yields compared to liquid targets, owing to the denser ⁶⁸Zn target material and superior heat transfer to the target backing that enables greater cyclotron beam currents. The much higher yields obtained with solid targetry mitigate the short half-life of ⁶⁸Ga, enabling large-scale distribution of ⁶⁸Ga to other PET centers surrounding a cyclotron facility.

In case of a solid target technology, like the Alceo system, Comecer has a special hot cells to handle the solid target modules:

Radiolabeling with ⁶⁸Ga is a single-step synthetic process that can be executed in three ways. ⁶⁸Ga-radiopharmaceuticals can be produced either manually, by (semi)automated processes or by using a cold kit. A disadvantage of manual production is the manipulation of significant ⁶⁸Ga activities near unshielded hands. The hands of the operator can be only protected from radioactive contamination by gloves, and from dose by extending the distance to the source of radioactivity with tweezers or tongs. Consequently, manual preparation results in high finger dose exposures for the operator. For example, the estimated absorbed body and hand dose for the manual synthesis of [⁶⁸Ga]Ga-DOTA-TATE was 2.0 and 27 μSv, respectively, while compared to an automated synthesis it was 1.3 and 7.9 μSv, respectively. Additional disadvantages are inconsistent radiochemical purities and/or radiochemical yields between productions and potentially non-GMP compliant processes, which is not acceptable for translation to a clinical setting.

The key advantage of maintaining full manual control of the radiolabeling process is its usefulness for the early development of radiopharmaceuticals for research purposes. Studies regarding labeling kinetics and radiopharmaceutical stability can be performed, while keeping the hand dose low. Those labeling studies can be performed with lower radioactivity concentrations to minimize operator dose (< 100 MBq versus 1–2 GBq used for clinical application).
Even for the labelling processes a hot cell is needed. Comecer can offer different solutions:

• when a generator or a liquid target to produce 68Ga is used, and so the radioactivity levels are not so high, a Thecla is the perfect hot cell to accommodate a synthesis module;
• in case of a solid target production followed by a labeling, where we can start from 2Ci of 68Ga, a BBS hot cell is needed. The BBS Series has a higher shielding and can protect the operators from the high doses used.

The advent of commercial 68Ge/68Ga generator suppliers in multiple countries combined with PET centers implementing ⁶⁸Ga cyclotron production has significantly improved the availability of ⁶⁸Ga and enabled widespread use in research and the clinic. Recent high yield ⁶⁸Ga cyclotron production could enable distribution to smaller communities surrounding cyclotron facilities, improving patient accessibility to diagnostic scans, provided that 66Ga/67Ga impurities in the ⁶⁸Ga product are within regulatory limits. A potential advantage of distributing ⁶⁸Ga activity from a cyclotron facility to smaller surrounding PET centers is lower shielding and processing space requirements associated with producing ⁶⁸Ga radiopharmaceuticals on site from scratch using a 68Ge/68Ga generator.
Additionally, the widespread availability of ⁶⁸Ga has resulted in its increasing use as a diagnostic radionuclide partner for nuclear medicine theranostics, highlighted by prostate cancer clinical trials using [⁶⁸Ga]Ga-PSMA compounds as a diagnostic imaging agent for [¹⁷⁷Lu]Lu-PSMA or [²²⁵Ac]Ac-PSMA therapy, and [⁶⁸Ga]Ga-DOTATATE used to track [¹⁷⁷Lu]Lu-DOTATATE or [²²⁵Ac]Ac-DOTATATE therapy of neuroendocrine tumors. Since the demand for targeted radionuclide therapies is increasing rapidly, it can be expected that the demand for 68Ga theranostic imaging agents will continue to increase.

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