Ilic Vesna, Dunet Vincent, Le Pape Alain, Buchs Mikael, Kosinski Marek, Bischof Delaloye Angelika, Gerber Stefan, Prior John O
Prof. John O. Prior, PhD MD, Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Rue du Bugnon 46, 1011 Lausanne, Switzerland, Tel. +41/21/314 43-48, Fax -49,
Nuklearmedizin. 2016 Sep 26;55(5):203-8. doi: 10.3413/Nukmed-0811-16-03. Epub 2016 Jul 21.
Vaccination by aerosol inhalation can be used to efficiently deliver antigen against HPV to mucosal tissue, which is particularly useful in developing countries (simplicity of administration, costs, no need for cold chain). For optimal immunological response, vaccine particles should preferentially be delivered to proximal bronchial airways. We aimed at quantifying the deposition of inhaled particles in central airways and peripheral lung, and to assess administration biosafety. Participants, methods: 20 healthy volunteers (13W/7M, aged 24±4y) performed a 10-min free-breathing inhalation of (99m)Tc-stannous chloride colloid aerosol (450 MBq) in a buffer solution without vaccinal particles using an ultrasonic nebulizer (mass median aerodynamic diameter 4.2 μm) and a double mask inside a biosafety cabinet dedicated to assess environmental particle release. SPECT/CT and whole-body planar scintigraphy were acquired to determine whole-body and regional C/P distribution ratio (central-to-peripheral pulmonary deposition counts). Using a phantom, SPECT sensitivity was calibrated to obtain absolute pulmonary activity deposited by inhalation.
All participants successfully performed the inhalation that was well tolerated (no change in pulmonary peak expiratory flow rate, p = 0.9). It was environmentally safe (no activity released in the biosafety filter.) 1.3±0.6% (range 0.4-2.6%) of the total nebulizer activity was deposited in the lungs with a C/P distribution ratio of 0.40±0.20 (range 0.15-1.14).
Quantification and regional distribution of inhaled particles in an aerosolized vaccine model is possible using radioactive particles. This will allow optimizing deposition parameters and determining the particles charge for active-particles vaccination.
通过气溶胶吸入进行疫苗接种可有效地将针对人乳头瘤病毒(HPV)的抗原递送至粘膜组织,这在发展中国家尤为有用(给药简便、成本低、无需冷链)。为实现最佳免疫反应,疫苗颗粒应优先递送至近端支气管气道。我们旨在量化吸入颗粒在中央气道和外周肺中的沉积,并评估给药的生物安全性。
参与者、方法:20名健康志愿者(13名女性/7名男性,年龄24±4岁)在生物安全柜内,使用超声雾化器(质量中值空气动力学直径4.2μm)和双层面罩,在不含疫苗颗粒的缓冲溶液中自由呼吸吸入(99m)锝氯化亚锡胶体气溶胶(450MBq)10分钟,该生物安全柜专门用于评估环境颗粒释放。采集单光子发射计算机断层扫描/计算机断层扫描(SPECT/CT)和全身平面闪烁扫描,以确定全身和区域的中央与外周肺沉积计数(C/P)分布比。使用体模对SPECT灵敏度进行校准,以获得吸入后沉积的绝对肺活度。
所有参与者均成功完成吸入,耐受性良好(肺峰值呼气流量无变化,p = 0.9)。对环境安全(生物安全过滤器中无活度释放)。雾化器总活度的1.3±0.6%(范围0.4 - 2.6%)沉积在肺部,C/P分布比为0.40±0.20(范围0.15 - 1.14)。
使用放射性颗粒可以对雾化疫苗模型中吸入颗粒进行定量和区域分布分析。这将有助于优化沉积参数,并确定活性颗粒疫苗接种的颗粒电荷。