title: SPECT/CT study of bronchial deposition of inhaled particles. A human aerosol vaccination model against HPV.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.forename: Vesna
authors.initials: V
authors.lastname: Ilic
authors.forename: Vincent
authors.initials: V
authors.lastname: Dunet
authors.forename: Alain
authors.initials: A
authors.lastname: Le Pape
authors.forename: Mikael
authors.initials: M
authors.lastname: Buchs
authors.forename: Marek
authors.initials: M
authors.lastname: Kosinski
authors.forename: Angelika
authors.initials: A
authors.lastname: Bischof Delaloye
authors.forename: Stefan
authors.initials: S
authors.lastname: Gerber
authors.affiliation: 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, john.prior@chuv.ch.
authors.forename: John O
authors.initials: JO
authors.lastname: Prior
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001980:Bronchi / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007553:Isotope Labeling; D008297:Male; D030361:Papillomavirus Infections / Q000378:metabolism / Q000517:prevention & control; D053918:Papillomavirus Vaccines / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D000072098:Single Photon Emission Computed Tomography Computed Tomography / Q000379:methods*; D013667:Technetium / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D000336:Aerosols; D053918:Papillomavirus Vaccines; D019275:Radiopharmaceuticals; D013667:Technetium
keywords: 99mTc; Aerosol inhalation; HPV; SPECT/CT; pulmonary deposition; targeted vaccine delivery