Pharmaceutical preparation of oxygen-15 labelled molecular oxygen and carbon monoxide gasses in a hospital setting

BACKGROUND: Clinical positron emission tomography (PET) requires safe and effective PET radiopharmaceuticals. Tracers used for measuring oxygen consumption and blood volume are [(15)O]O(2) and [(15)O]CO, respectively. In general, these oxygen-15 labelled tracers are produced using a cyclotron that accelerates deuterons onto a target filled with (14)N(2) containing a trace of oxygen. In recent years, cyclotrons have been developed that only are capable of accelerating protons. The purpose of this study was to validate and assess such a cyclotron for production and administration of oxygen-15 labelled gasses in an hospital setting. METHODS: An RDS111 cyclotron (Siemens-CTI, Knoxville, USA) was validated for bolus production of [(15)O]O(2) and [(15)O]CO gasses. In addition, equipment was developed to administer these tracers to patients. RESULTS: Both [(15)O]O(2) and [(15)O]CO gasses could be produced in sufficient amounts, whilst meeting European Pharmacopeia requirements. Although produced oxygen-15 gasses contained a minor level of (11)C contamination, in clinical studies it was possible to correct for this contamination by delayed blood counting. CONCLUSION: An 11 MeV proton cyclotron combined with an in-house developed gas delivery system allows for the production and administration of sufficient amounts of [(15)O]-gasses for routine clinical PET studies in an hospital setting.