George Herbert1,2, Glenn Woolley1,2,3, Dave Roberts1,2, Juozas Domarkas1,2, John Wright1,2, Graham Wright3 & Stephen J. Archibald1,2
1Department of Biomedical Sciences, The University of Hull, Cottingham Road, Hull, HU6 7RX, UK
2The Positron Emission Tomography Research Centre, The University of Hull, Cottingham Road, Hull, HU6 7RX, UK
3Hull University Teaching Hospitals NHS Trust, Castle Hill Hospital, Castle Road, Cottingham, HU16 5JQ, UK
Summary
Positron emission tomography (PET) is a highly sensitive and quantitative modality that can be employed for the efficient and informed development of novel pulmonary drug delivery devices. Vape devices present an alternate drug delivery system whereby the performance and formulation can be personalised for the end-user to improve experience and compliance. A novel molecule was designed, synthesised and radiolabelled to allow efficient radiolabelling of vape liquid. This probe was used to understand the influence of device settings on output. It was concluded that a high a temperature setpoint (315˚C), low coil resistance (< 0.3 Ω) and short vape duration (≤ 4s) greatly increased output whilst flow rate (2.3 – 35 L/min) and glycerol content (0 – 100%) had little influence. Optimal settings were used to demonstrate marked increase in output efficiency of vape devices (10.91%/s) compared to jet nebulisers (0.18%/s). Using these settings, two known radiolabelled drug candidates ([18F]Fluticasone propionate and [18F]Fleroxacin) were assessed for their respective output and stability. [18F]Fluticasone propionate demonstrated good output (4.08%/s) and stability at the highest temperature setting; these promising results warrant further investigation. [18F]Fleroxacin was unstable at higher temperature and required vaping at 100˚C to maintain drug integrity; output was compromised and it was concluded that this drug class was unsuitable for vape delivery. A mass median aerodynamic diameter of 1 µm and comparative activity distribution of vaped radiotracers confirmed uniform dispersion within the vape liquid and the capability for deep lung delivery using vape devices.
Key Message
The sensitive and quantitative properties of fluorine-18 radiolabelling were used to validate vape devices as novel drug delivery systems. The parameters for optimal output were determined and used to demonstrate significantly improved performance compared to a jet nebuliser. Favourable output and stability were observed for a clinically relevant radiolabelled corticosteroid.