Solutions of Cu-64 and Ga-68 Produced Inside the Cyclotron Self-shield using a Dual Function Solid Target System

Introduction: The potential of PET imaging using metallic radioisotopes such as Cu-64 and Ga-68 is already well recognized yet limited, in part, due to the availability of suitable production systems. Most PET cyclotrons and facilities are designed for the irradiation of F-18 water or gas targets to be installed inside the self-shield and the their radioactive content to be handle by thin tubing. However, commercially available solid targets are comprised of bulky handling mechanisms that requires walls with openings for the passage of thick air shuttles, not to mention they are rather expensive. We aimed to sort out these issues by creating the concept of an irradiation and dissolution target system that is installed inside the self-shield and that allows the transfer of the irradiated material to the hot cell as a solution. In this work, we designed a F-18 water target-like niobium vessel containing a solid target that is irradiated and then remotely docked to a dissolution port using the built-in automatic target changer of the CYPRIS^Ò HM-12 cyclotron. This target with irradiation and dissolution dual functions was used for the in-situ production of Cu-64 or Ga-68 solutions.

Methods: Cu-64 and Ga-68 were produced by the proton irradiation (11.8 MeV on target) of enriched Ni-64 or Zn-68, respectively as reported elsewhere.

The target assembly consists of a front hollowed vessel made of niobium and a back flange made of aluminum. Gold or silver plates containing the target materials are sandwiched at a 30-degree slope between the two flanges and sealed using O-rings. A water jet located inside the back flange directly cools the target plate. Helium gas is used to cool the vacuum foil and the surface of the target materials simultaneously.

The target assembly is removed from the target port after irradiation and docked through the front niobium vessel to a dissolution port. HCl is then injected to dissolve the targets materials through apertures created inside the port. In the case of Ni-64, a miniature ceramic heater is also used. The solution is then transferred to a collection vial in the hot cell. The target assembly is only removed from the dissolution port once all the lines are thoroughly washed with water.

Results: Irradiations with 40 mA of beam current were successfully performed on both Ni-64 and Zn-68 targets. Visual inspection of the unprocessed plate didn’t show any sign of heat damage. Shifting from the irradiation position to dissolution position took place short after stopping the beam and acid was injected once adequate sealing was confirmed by a quick leak test.

Production tests were aimed to investigate target yields of the transferred solutions. The Cu-64 EOB yield averaged 0.09±0.01 GBq/mAh (42.0±3 mg). A typical 6 h irradiation at 40 mA would yield 17.7 GBq of activity. The EOB yield of Ga-68 was 0.71±0.12 GBq/mAh (42.0±8 mg). This would provide 20.8 GBq from 60 min irradiation at 40 mA. Increasing target material and beam current would further increase these yields several folds.

Conclusions: A solid target system based on a niobium vessel with dual irradiation and dissolution functions was developed and tested. Solutions of ready to be purified Cu-64 and Ga-68 were produced in high yield enough to satisfy the in-house demand of these radionuclides and others such as Zr-89. The installation is simple, no special building requirements, hot cell space saving and GMP amenable. In general, the present system is a more viable alternative to other commercially available systems.

Acknowledgments: We want to thank Medical Imaging Center for Translational Research, Graduate school of Medicine, Osaka University for the contribution to this work.