Production of Metallic Radionuclides at Sumitomo CYPRIS HM-10 Cyclotron Using an Automatic Irradiation and Dissolution Target System

Objectives: Metallic Radionuclides are of great interest for radiopeptide and/or radioimmuno imaging as well as for theranostic uses. They can be produced using solid or liquid targets. However, solid target systems might comprise a costly and space demanding automatic transport system for the transfer of the irradiated target. Furthermore, their pneumatic components affect the air cleanliness of GMP areas. Manual transportation systems, on the other hand, pose the problem of radiation exposure during handling and it is not suitable for short half-lived radioisotopes. Sumitomo CYPRIS HM-10 is a compact, low energy cyclotron for the production of FDG and others radiopharmaceuticals. Given the high demand, it has become imperative the availability of metallic radioisotopes even at the small hospitals where CYPRIS HM-10 is usually installed. However, in addition to the issues mentioned above, production of metallic radionuclides has been limited to proton energies above 10 MeV. Similarly, liquid targets choice is not viable due to impractical low yields at low energies. Considering the above we aimed to develop 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. This work presents the first production results of Cu-64, Zr-89 and Ga-68.

Methods: The target plate is initially placed on a horizontal transport holder that automatically moves up to the irradiation port. During irradiation the bottom side of the plate containing the target material is cooled by a stream of water and the top side by helium. After bombardment using a slanting beam, the plate is transported and set inside the dissolution vessel located next to the irradiation port. The vessel itself is enclosed by a box that is kept under negative pressure to avoid the release of any acidic fume to the cyclotron surrounding. Acid is remotely injected and the target material is then transferred to the hot cell as a solution once dissolution has proceeded. Finally all the line is washed thoroughly. All the operations are performed remotely and both PC and wireless tablet operated. The ⁶⁴Ni(p,n)⁶⁴Cu, ^natY(p,n)⁸⁹Zr and ⁶⁸Zn(p,n)⁶⁸Ga nuclear reactions were used for the production of Cu-64, Zr-89 and Ga-68, respectively. Target materials were fixed onto a gold plate either by electrodeposition (Cu-64 and Ga-68) or by simple foil insertion (Zr-89). Irradiations were carried out with beams of 9.4 MeV on target energy, 20~30 μA of current, during 30~180 min depending on the radionuclide. After irradiation, the target material was dissolved in 2 mL of HCl at a concentration of 6 M with heating at 165 °C for Ni-64 and at r.t. for Y foil, and 10 M at r.t. for Zn-68.

Results: More than 20 μA of beam current was used and no damage of the target material or surrounding was observed. Disk transfer and dissolution were smooth, and the target solution could be transferred to the hot cell through 20 m of PTFE piping. Under the conditions used, up to 2.86 GBq (77.2 mCi) of Cu-64, 1.13 GBq (30.5 mCi) of Zr-89 and 10.4 GBq (280 mCi) of Ga-68 could be produced. The radionuclides were obtained at high yields considering the low energy of the beam used. The processing time was short, requiring only 25 min to collect the solution of the time sensitive Ga-68.

Conclusions: The production of Cu-64, Zr-89 and Ga-68 was successfully carried out at the low energy cyclotron CYPRIS HM-10 using a newly developed target system. The system is compact and can be co-located with three more liquid or gas targets for the short-lived F-18, N-13 or C-11. All the production was performed remotely, with minimum radiation exposure. Additionally, similar to F-18, the system is GMP compatible. The optimization of production conditions to maximize the yield is undergoing. This method will make metallic radioisotopes available to small hospitals. Acknowledgments: We want to thank HK AMS Limited for the contribution to this work.