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

Abstract

Background15O-oxygen inhalation PET is unique in its ability to provide fundamental information regarding cerebral hemodynamics and energy metabolism in man. However, the use of 15O-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 15O-labeled gaseous radiopharmaceuticals of C15O, 15O2, and C15O2 at short intervals.MethodsThe system consists of a radiosynthesizer which produces C15O, 15O2, and C15O2; 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.ResultsUsing an 15O-dedicated cyclotron with deuteron of 3.5 MeV at 40 μA, C15O, 15O2, and C15O2 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 C15O, and 1-min supply of 2220 ± 766 and 1763 ± 174 for 15O2 and C15O2, respectively.ConclusionsThe present system allowed for automated production and inhalation of series of 15O-labeled radiopharmaceuticals as required in the rapid 15O-Oxygen PET protocol. The production and inhalation were reproducible and improved logistical complexity, and thus the use of 15O-oxygen might have become practically applicable in clinical environments.

Quantification of brain oxygen extraction and metabolism with [15O]-gas PET: A technical review in the era of PET/MRI

“…For instance, some sites have cyclotrons that are located up to several thousand feet from the scanner, and require shielded delivery through pneumatic tubes and an inhalation controller at the scanner location. The inhalation controller is a circuit that regulates the gas tracer delivery rate and consists of components such as a mass flow controller, a radioactive detector, and a flow meter ( Iguchi et al, 2018 ). Investigators should check for gas leaks using the flow meter and a test carrier gas before the start of each experiment.…”

“…The participants may be similarly prompted to exhale deeply back into the respiration bag, to measure and subtract out any residual, exhaled tracer and safely contain it. Depending on local and health physics safety requirements, the air of the entire PET room may be exhausted at a rate of up to 20 complete air changes per hour ( Iguchi et al, 2018 ). This air flow ensures that exhaled or leaked gas tracer does not become trapped in the scanner facility and add unnecessary radiation to the subject or to investigators.…”

“…(b) Physiological corrections include modeling of the tracer in the blood pool through a separate image of cerebral blood volume ( Okazawa et al, 2001b ). Tissue heterogeneity ( Bremmer et al, 2011 ; Iguchi et al, 2018 ), i.e. the presence of multiple tissue types within a single voxel, is also a critical physiological concern especially for conditions of low perfusion and low OEF where comparatively little [ 15 O]-oxygen tracer is extracted.…”

Neuroimaging Methods to Map In Vivo Changes of OXPHOS and Oxidative Stress in Neurodegenerative Disorders

“…In addition, handling gaseous radioactive tracers raises safety concerns that need to be addressed. Shielding devices and gamma camera-controlled exhaust systems for the scanner room have been successfully employed in the past [89].…”

EANM procedural guidelines for PET/CT quantitative myocardial perfusion imaging

“…15 O is produced either by irradiating enriched Nitrogen-15 ( 15 N) with protons, using the 15 N(p,n) 15 O reaction, or by irradiating natural nitrogen with deuterons using the 14 N(d,n) 15 O reaction. The advantage of the latter production method is that the target material is basically air and, hence, cheap and that the required deuteron energy is only 3 MeV, allowing for construction of small, dedicated cyclotrons requiring limited shielding, at a considerably lower cost than regular PET cyclotrons [ 19 ]. These cyclotrons have until now only been installed at a few mainly research hospitals, but their wider spread could facilitate an increased clinical use of [ 15 O]water.…”