System evaluation of automated production and inhalation of (15)O-labeled gaseous radiopharmaceuticals for the rapid (15)O-oxygen PET examinations

BACKGROUND: (15)O-oxygen inhalation PET is unique in its ability to provide fundamental information regarding cerebral hemodynamics and energy metabolism in man. However, the use of (15)O-oxygen has been limited in a clinical environment largely attributed to logistical complexity, in relation to a long study period, and the need to produce and inhale three sets of radiopharmaceuticals. Despite the recent works that enabled shortening of the PET examination period, radiopharmaceutical production has still been a limiting factor. This study was aimed to evaluate a recently developed radiosynthesis/inhalation system that automatically supplies a series of (15)O-labeled gaseous radiopharmaceuticals of C(15)O, (15)O(2), and C(15)O(2) at short intervals. METHODS: The system consists of a radiosynthesizer which produces C(15)O, (15)O(2), and C(15)O(2); an inhalation controller; and an inhalation/scavenging unit. All three parts are controlled by a common sequencer, enabling automated production and inhalation at intervals less than 4.5 min. The gas inhalation/scavenging unit controls to sequentially supply of qualified radiopharmaceuticals at given radioactivity for given periods at given intervals. The unit also scavenges effectively the non-inhaled radioactive gases. Performance and reproducibility are evaluated. RESULTS: Using an (15)O-dedicated cyclotron with deuteron of 3.5 MeV at 40 μA, C(15)O, (15)O(2), and C(15)O(2) were sequentially produced at a constant rate of 1400, 2400, and 2000 MBq/min, respectively. Each of radiopharmaceuticals were stably inhaled at < 4.5 min intervals with negligible contamination from the previous supply. The two-hole two-layered face mask with scavenging device minimized the gaseous radioactivity surrounding subject’s face, while maintaining the normocapnia during examination periods. Quantitative assessment of net administration doses could be assessed using a pair of radio-detectors at inlet and scavenging tubes, as 541 ± 149, 320 ± 103, 523 ± 137 MBq corresponding to 2-min supply of 2574 ± 255 MBq for C(15)O, and 1-min supply of 2220 ± 766 and 1763 ± 174 for (15)O(2) and C(15)O(2), respectively. CONCLUSIONS: The present system allowed for automated production and inhalation of series of (15)O-labeled radiopharmaceuticals as required in the rapid (15)O-Oxygen PET protocol. The production and inhalation were reproducible and improved logistical complexity, and thus the use of (15)O-oxygen might have become practically applicable in clinical environments.