Aiman H. Alnahwi et al. [16] developed an automated ⁶⁸Ga[Ga] radiosynthesis for routine large-scale production using a squeezed ⁶⁸Zn[Zn] target (target highly enriched to 99.26 in ⁶⁸Zn[Zn]) (Table 2).

Thus, ⁶⁸Zn[Zn] pellets of different diameter and thickness were prepared (diameter: 6 to 10 mm and thickness: 0.51 to 0.55 mm). The target carrier was made of aluminum, so it was only weakly activated by the proton beam from the cyclotron according to these authors. In addition, aluminum, due to its thermal conductivity properties [17] [18], allowed efficient cooling of the target during irradiation.

In another study, Lin et al. [8] used an enriched ⁶⁸Zn[Zn] target (60 - 120 mg) with a diameter of 7 mm. The target was electrodeposited on a platinum disc and then it was transferred and mounted in the cyclotron PETtrace via the module Comecer EDS/PTS (Castel Bolognese RA, Italy).

Aiman H. Alnahwi et al. [16] used irradiations with a beam current between 5 and 35 μA on the squeezed ⁶⁸Zn[Zn] target with an energy ranging from 13 to 14.5 MeV for a duration of 90 minutes. The irradiations were first carried out on a 6 mm target for which the production yield (corrected for the decay) was 2.6 GBq/μA·h. The activity of ⁶⁸Ga[Ga] increased when the current applied to the target was greater (input 1 - 3). The highest production yields were obtained with the 8- and 10-mm targets (entries 4 - 5). Using a current of 35 μA, 145 ± 6 GBq (at EOB: end of bombardment) was produced (input 6) (Table 3). This value (145 ± 6 GBq in EOB) is superior to the values reported by Lin et al. (Lin, Waligorski, et Lepera 2018) which used an incident energy of 14.5 MeV proton beam with beam currents of 15 à 40 μA and a power equivalent to about 80 times the activity of a generator.

Other authors like Sadeghi et al. [13] obtained interesting yield values for the ⁶⁸Zn[Zn] (p, n) ⁶⁸Ga[Ga] nuclear reaction using a solid target of Zn enriched to 97% in ⁶⁸Zn[Zn]. Their EOB yield reached 5.032 GBq/μAh at 15 MeV with the use of a target of 52 μm thick; with an irradiation time of 0.25 h and a beam current of 150 μA. Szelecsényi et al. [11] reported that their values, calculated with the cross sections (5.809 GBq/μAh), were in agreement with these data.

After facilitated transport via magnetic media (Automated Target Transfer System [12] ), immediate dissolution of the target should be performed for rapid transfer to the purification column. 7N nitric acid HNO₃ can be used for target dissolution. Another particularly interesting method for extracting radioisotopes of gallium from zinc targets is the thermal diffusion method described by Tolmachev and Lundqvist [19]. A similar method was also employed by Zeisler et al. [20].

^aThe proton beam energies were calculated by Monte Carlo simulation using SRIM. Irradiation time was fixed at 30 min. ^bTotal recovered activity, corrected at EOB. ^cIrradiation time was 90 min. ^dSaturation yield estimated from results reported by Lin et al. [8]. Entries 1 - 5, n = 1; entry 6, n = 2.

The automated purification process implemented by Aiman H. Alnahwi et al. [16] used a hydroxamate resin. 0.01 N HCl solution (50 mL) was required to remove ⁶⁸Zn[Zn]. The ⁶⁸Ga[Ga] was then eluted from the hydroxamate resin with 0.75 N HCl as [⁶⁸Ga] GaCl₃. This provides ⁶⁸Ga[Ga] with a high radiochemical yield and a lead time of the dissolution and purification method of less than 10 - 12 min (20 min for Lin et al. [8] ). The last purification step, carried out with the CUBCX resin [21], has already been validated internally.

Aiman H. Alnahwi et al. [16] described the presence of metal impurities after purification. For all batches tested, metallic impurities were below the general limit of 10 ppm and 20 ppm for heavy metals (USP and Ph. Eur.). The concentrations of impurities of antimony, barium, beryllium, bismuth, cadmium, chromium, cobalt, lead, lithium, molybdenum, selenium, silver, tin, titanium, vanadium were <0.5 ppm. The elements Al, Fe, Mg, Zn and Cu were <4 ppm.

The main isotopic impurities were identified by gamma spectrometry (29, 50 and 72 h post purification) and consisted of ⁶⁷Ga[Ga] (physical period: 3.26 days) and ⁶⁶Ga[Ga] (physical period: 9.45 h), as indicated previously by Al-Saleh et al. [22] [23] and their total combined amount was less than 2% at 6 h after irradiation (Energy 13 MeV). ⁶⁷Ga[Ga] can be produced via the reactions ⁶⁷Zn[Zn] (p, n) ⁶⁷Ga[Ga] and ⁶⁸Zn[Zn] (p, 2n) ⁶⁷Ga[Ga] with incident proton energy of 2 - 26 MeV and 13 - 29.5 MeV, respectively. ⁶⁶Ga[Ga] can be produced via ⁶⁶Zn[Zn] (p, n) ⁶⁶Ga[Ga] and ⁶⁷Zn[Zn] (p, 2n) ⁶⁶Ga[Ga] with incident particle energy of 6 - 26 MeV and 15 - 26 MeV, respectively [24]. According to the experimental measurements reported by Alves et al. [5], the amounts of ⁶⁷Ga[Ga] and ⁶⁶Ga[Ga] can be kept below 2% using a particle energy of 13 MeV. For example, the ⁶⁸Ga[Ga] purities may be 99.97% and 99.99% at EOB for particle energies of 14 and 13 MeV respectively. These values were confirmed by Lin et al. [8] who observed a small fraction (≤0.2%) of ⁶⁷Ga[Ga] when the target was irradiated for up to 90 min with 14.5 MeV protons.

Many authors have not performed a target recovery process, believing it to be more expensive than buying a new target. However, according to an IAEA document [12], ⁶⁸Zn[Zn] can easily be recovered provided no impurities (e.g. iron) are present. Thus, simple multiple drying with nitric acid can be performed as described below. The procedure includes: 1) dry evaporation; 2) Dilution in concentrated nitric acid (>10 M); 3) Repeat the evaporation; 4) Dilution in 10 mM nitric acid; and 5) Evaporation to dryness or preparation of a ready-to-use solution. >90% recovery of the ⁶⁸Zn isotope of Zinc is expected. All reagents used must be of high quality, traces of metal.

Buying a new target is worth more than this long and tedious target recovery process.