ABSTRACT

A new production method of no-carrier-added ⁶⁴Cu was tested using a new target prepared by electroplating of Ni on a silver layer (thickness 35 µm) previously electroplated on a pure copper target support. This method meets cost effective production and quality of the produced ⁶⁴Cu criteria. The quality of the electroplated layers has been tested under the bombardment by more than 200 µA of proton beam using water cooled target system. A separation and purification setup was elaborated to produce high quantity and high specific activity of ⁶⁴CuCl₂ suitable for labeling different ligands in order to be used in therapy and diagnosis. A semi-automated target dissolution and separation system has been developed and achieved for ⁶⁴Cu production. The separation chemistry is based on a chromatographic column system.

1. Introduction

The radionuclide ⁶⁴Cu (T_1/2 = 12.7 h) emits β⁻ 39% and β⁺ 17.4% (;= 573 KeV). These characteristics make it useful for both high resolution PET imaging and targeted endoradiotherapy. In addition, its electron capture decay associated with Auger emission gives more efficient cell killing when this radioisotope is deposited in the cell [1].

Another advantage of this important radionuclide is the stability of its complexes with bifunctional chelators consisting of the metal complex ligand and the functional group for attachment to the targeting molecule [2].

Until now ⁶⁴Cu-ATSM is the most investigated radiolabeled compound and it seems to be a promising agent for endoradiotherapy [3-5].

Many methods for the production of ⁶⁴Cu have been investigated; 1) based on low energy cyclotron via the nuclear reaction ⁶⁴Ni (p, n) ⁶⁴Cu [6-9], 2) proton irradiation of enriched ⁶⁸Zn using the nuclear reaction ⁶⁸Zn (p, αn) ⁶⁴Cu as a side reaction in the production of ⁶⁷Ga [10,11]. In the first method Ni is electroplated on gold disk. Due to the fact that target support (gold disk) can be used for one time and irradiation beam intensity used for this target support is very low resulting low quantity of the produced ⁶⁴Cu radioactivity. In this study, we would like to prove that high quality and quantity of ⁶⁴Cu can be produced using a new target prepared by the electroplating of Ni on silver layer previously electroplated on a pure copper target support. Then we describe an effective set up for the separation and purification of ⁶⁴Cu from the irradiated target. Also a quality control of the produced radioactive copper is carried out.

2. Materials and Methods

The nickel nitrate Ni(NO₃)₂∙6H₂O (purity 99%, GR) was purchased from Merck. AgNO₃ (purity 99.9%, GR) was purchased from BDH. Hydrochloric acid (GR) was purchased from Merck. Ion exchange resin (Dowex 1 × 8) was bought from Sigma-Aldrich.

Radioisotopes were identified by gamma spectrometry using a high purity germanium (HPGe) detector with 25% efficiency, where the amplifier output of the detector was processed by a 4096 channels multi-channel analyzer (MCA) system. The fitting program (INTER WINER) was used for spectral data processing.

Developed anodic stripping voltammetry system purchased from Metrohm (VA processor 693 with VA stand 694) was used for trace metals analysis in the produced Cu bulk. This system uses a working electrode (Hanging Mercury Dropped Electrode (HMDE)), a reference electrode Ag/AgCl/KCl (3 mol) and an auxiliary electrode from platinum.

The electroplating is carried out on copper target support, (2 × 10 cm), designed by IBA. The blank cooper target is back water cooled and designed to be irradiated with more than 300 µA at 30 MeV proton beam.

3. Results and Discussion

The production process of ⁶⁴Cu was performed according to the block diagram presented in Figure 1.

3.1. Target Support Electroplating

The surface of the copper target support, (2 × 10 cm), was cleaned by fine abrasive wool and acetone. This surface was electroplated by silver using (AgNO₃, NaCN and Na₂CO₃) bath having pH ≥ 12 at room temperature. The voltage and current density used for silver electroplating were 4 V and 4 mA/cm² respectively. The thickness of the electroplated silver layer was calculated to be 35 µm.

The function of the electroplated silver layer is to prevent the dissolution of copper target support in order to produce non-carrier added ⁶⁴Cu.

On the silver layer, natural nickel was electroplated on a smaller surface (1 × 10 cm) using [Ni(NO₃)₂, Na₂SO₄, NH₄Cl and H₃BO₄] bath having pH ≈ 9 at room temperature. The voltage and current density for Ni electroplating was 6 V and 50 mA/cm² and the electroplated thickness was about 12 µm. Figures 2-4 show the electroplated target and target surface.

3.2. Target Irradiation

The electroplated target was irradiated by a 15 MeV proton beam of 200 μA intensity using Cyclone-30 cyclotron (IBA, Belgium) during 3 h. The back side of the target was cooled with a very high speed stream of deionized water flowing through IBA irradiation station. No any damage on electroplated target has been noticed. Which prove that the two electroplated layers stick very well on the copper substrate (Figure 5).

Different isotopes can be produced after the proton irradiation of our target.

Table 1 summarizes production conditions and the characteristics of the resulting isotopes in our target.

Table 1. Reaction cross sections, threshold energies thick target yields and radiation characteristics of the reaction products.

The irradiated target has been dissolved in concentrated hydrochloric acid under heating to 90˚C. Figure 6 shows the target dissolution unit used in this study. The dissolution speed is increased by adding 500 µl of hydrogen peroxide if necessary.

The resulting solution contains ^*Cu, ^*Ni, ^*Co, ^*Cd and traces of silver. A column (150 × 10 mm) containing Dowex 1 × 8 was conditioned by 30 ml of HCl 9 N and used for the separation and purification of ⁶⁴Cu.

The resulting solution was passed through the separation column using flow rate 2.5 ml/min. All nickel and trace silver are removed from the column by 30 ml HCl 9 N, flow rate 2.5 ml/min. Figure 7 shows the separation and purification unit.

Then Cu-64 is eluted from the column by 20 ml of deionized water. The elution profile of Ni and ⁶⁴Cu are shown in Figures 8 and 9.

Radioactive cobalt will remain in the resin; to be eluted it would need larger amount of water.

The produced ¹⁰⁹Cd formed from the nuclear reaction ¹⁰⁹Ag(p, n)¹⁰⁹Cd and all cobalt radioisotopes will be fixed in the column at the end of the two successive elutions (HCl 9 N and deionized water). For removing these isotopes from the resin, HCl of 12 N is used.

4. Quality Control of the Produced Radioactive Copper

As mentioned, we used natural Ni for the production of radioactive copper. Since natural nickel contains different Ni isotopes the proton irradiation will lead to the formation of ⁶⁰Cu, ⁶⁴Cu, ⁶¹Cu, ⁵⁶Ni, ⁵⁷Ni, ⁵⁵Co, ⁵⁶Co, ⁵⁷Co

and ⁵⁸Co.

The efficiency of the proposed separation and purification method is demonstrated by gamma spectrum shown in Figure 10. This figure shows that no other radioactive tracers formed in the target are present in separated solution of ⁶⁴Cu. This method of separation is valuable even when none highly enriched ⁶⁴Ni is used for the production of high quality ⁶⁴Cu.

5. Recovery and Recycling of Ni

In case of the use of enriched Ni, recovery process should be used. In our proposed method Ni collected in HCl 9 N contains trace amount of silver. The presence of trace amount of silver induces no effect on the purity of ⁶⁴Cu due to the fact that the ¹⁰⁹Cd generated from the reaction ¹⁰⁹Ag (p, n) ¹⁰⁹Cd will be fixed on the ⁶⁴Cu separation column. The separation of Ni from silver is carried out using chromatographic column (150 × 20 mm) filled with the cation exchanger Dowex 50WX4. This column is preconditioned by 30 ml of HCl 2 N. The Ni and silver cation solution is adjusted to HCl 2 N.

Ag cation is removed from the column by HCl 2 N and then Ni cation can be recovered in a small volume by HCl 0.05 N.

Gamma spectrum of the separated Ni to be used for another Ni electroplating of a new target is shown in Figure 11. This figure shows no presence of radio-cobalt or radio-copper in the recovered Ni solution.

All radio-cobalt and radio-cadmium is fixed in the resin at the end of separation and purification. Gamma spectrum of the resin is shown in Figure 12.

6. Conclusion

Good quantity and high quality of ⁶⁴ Cu can be produced using electroplated enriched ⁶⁴Ni on silver layer previously electroplated on a pure copper target support. Chromatographic separation techniques have been used in order to separate high purity no carrier added ⁶⁴CuCl₂ suitable for labeling different ligands in order to be used in therapy and diagnosis. A semi-automated target dissolution and separation system has been developed and achieved for Cu-64 production. An efficient method to recover high costly enriched ⁶⁴Ni is also performed.

7. Acknowledgements

The authors are grateful to the IAEA for supporting this research through CRP 15937. Thanks to prof. I. Othman (GD of AECS) for the encouragement and support. Thanks to Raad A., Ibrahim W., Freihat S., Orabi H., Sahar M., Abdel hadi M. Abbas I., Al Enaya F., and Zakkar N. for their technical support.

REFERENCES

NOTES

^*Corresponding author.