All steps required for the production and separation of a metal radioisotope from a liquid target are implemented in a fully integrated system. For each isotope, a dedicated IBA Nirta Conical®
target system (IBA, Louvain-la-Neuve, Belgium) is used. To separate the metal isotopes from the target solution and reformulate them in a ready-to-use chloride solution, a commercially available IBA Synthera®
Extension module (IBA, Louvain-la-Neuve, Belgium) is used with single-use kits. For the radiolabelling step, an IBA Synthera®
Extension is used to label compounds with 64
Cu (e.g., bis(4-methyl-3-thiosemicarbazone), PTSM; diacetyl-2,3-bis(N4-methyl-3-thiosemicarbazone), ATSM) and an IBA [email protected]
Ga-based compounds (e.g., 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) peptides, N
′-diacetic acid (HBED) peptides. For metal trace analysis of samples, is used an inductively coupled plasma mass spectrometry (ICP-MS) equipment: Thermo Scientific iCAP Qc (Thermo Fisher Scientific, Waltham, MA, USA). To measure the activities of samples, an ISOMED 2010 (Nuklear-medizintechnik, Dresden, Germany) is used.
All chemicals and solvents used are trace-metal grade.
As target material, the enriched isotopes are diluted in a 0.01 M nitric acid solution (Table 1
). Concentrations are adjusted to produce a maximum of required activity while avoiding precipitation and providing stability of the solution over time for storage and better behaviour under the cyclotron beam without corrosion of target support materials [6
64Ni and 68Zn targets are typically irradiated with a beam current of about 70 µA and 45 µA, respectively, using an IBA 18/9 Cyclone cyclotron. The amount of enriched material on target varies from 10–100 mg of 64Ni and 100–400 mg of 68Zn, depending on the required activity. After irradiation, solutions are transferred to a processing hot-cell under nitrogen pressure.
For the Gallium-68 production, the irradiated 68
Zn target solution is dissolved multiple times in water and the solution is passed through a cation exchange resin (SCX; DOWEX 50W, 200–400 mesh, H+ form, treated with 10 mL of 3 M HCl followed by 10 mL of water) loaded on a 1 mL catridge. The cartridge is then washed with 30 mL of Acetone/HBr mixture to remove zinc ions as described by Strelow [21
]. The adsorbed 68
Ga cations are eluted from the SCX cartridge with 6 mL of HCl 3 M mixed with 10 mL of HCl 30% (to increase the molarity of HCl) to an intermediate reservoir (Figure 2
) and passed through an anion exchange resin (SAX; Biorad AG1 100 mesh, treated with 10 mL of water followed by 10 mL of HCl 8 M) loaded on 0.5 mL size-cartridge where the anionic complex [68
remained strongly adsorbed [23
]. A flow of inert gas is then applied to dry the column and remove any traces of HCl. Finally, 68
Ga is eluted from the column with water into a final collection vial in the form of 68
solution in 0.1–0.25 M HCl. The 68
Zn ions are collected on a separate vial and can be recycled to be reused as target material.
The entire purification process takes about 35 min from end of bombardment (EOB).
Conversely, for the production of copper radioisotopes (61
Cu and 64
Cu) the irradiated nat
Zn or 64
Ni liquid target solution is dissolved multiple times in water to bring the pH to a suitable range for the adsorption of the copper ions onto a highly selective Cu resin (TrisKem International, Bruz, France) loaded on 2 mL cartridge, as described by Dirks [25
]. The pH adjusted solution is then passed through the resin (pre-conditioned with 10 mL of water) that is then washed with 10 mL of HNO3
1 mM to remove any traces of non-copper ions. The adsorbed 64
Cu cations are eluted from the cartridge with 5 mL of HCl 3 M, directly to an anion exchange resin (SAX; TrisKem International, treated with 10 mL of water followed by 10 mL of HCl 8 M) (Figure 2
) loaded on 0.5 mL cartridge size where the anionic complex [64
remains strongly adsorbed. A flow of inert gas is then applied to dry the column and remove any traces of HCl. Finally, copper is eluted from the column with water into a final collection vial in the form of a copper chloride solution. In the case of 64
Cu production, 64
Ni ions are recovered on a separated vial and can be recovered to be recycled. As for nat
Zn, there is no need to recover, as natural zinc is quite inexpensive.
The entire purification process takes about 1 h from EOB.