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Nuklearmedizin 2016; 55(05): 203-208
DOI: 10.3413/Nukmed-0811-16-03
Original article
Schattauer GmbH

SPECT/CT study of bronchial deposition of inhaled particles

A human aerosol vaccination model against HPVSPECT/CT zum Nachweis von inhalierten PartikelnHumanes Modell zur inhalativen Vakzinierung gegen HPV
Vesna Ilic
1   Department of Nuclear Medicine, Lausanne University Hospital, Lausanne, Switzerland
,
Vincent Dunet
1   Department of Nuclear Medicine, Lausanne University Hospital, Lausanne, Switzerland
,
Alain Le Pape
2   Research Center for Respiratory Diseases, François Rabelais University, Tours, France
3   TAAM-CIPA, CNRS, Orléans, France
,
Mikael Buchs
1   Department of Nuclear Medicine, Lausanne University Hospital, Lausanne, Switzerland
,
Marek Kosinski
1   Department of Nuclear Medicine, Lausanne University Hospital, Lausanne, Switzerland
,
Angelika Bischof Delaloye
1   Department of Nuclear Medicine, Lausanne University Hospital, Lausanne, Switzerland
,
Stefan Gerber
4   Gynecology Practice, Fribourg, Switzerland
,
John O. Prior
1   Department of Nuclear Medicine, Lausanne University Hospital, Lausanne, Switzerland
› Author Affiliations
Further Information

Publication History

received: 19 March 2016

accepted in revised form: 28 June 2016

Publication Date:
20 December 2017 (online)

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Summary

Aims: 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 99mTc-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). Conclusion: 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.

Zusammenfassung

Die Entwicklung von Aerosol-Impfstoffen, damit durch Inhalation Antigene gegen HPV effizient im Schleimhautgewebe aufgenommen werden, könnte in Entwicklungsländern besonders wichtig sein (einfach zu applizieren, kostengünstig, kein Bedarf an Kühlkette, usw.). Um eine optimale immunologische Wirkung zu erzielen, sollte der inhalierte Impfstoff präferenziell in den proximalen Bronchien abgeschieden werden. Das Ziel dieser Studie war es, die Verteilung inhalierter Partikel in den zentralen Bronchien und in peripheren Lungenabschnitten zu messen und deren Biosicherheit zu bestimmen. Teilnehmer, Methode: 20 gesunde Versuchspersonen (13F/7M, 24±4Jahre) inhalierten während 10 Minuten unter Spontanatmung mittels eines Ultraschallverneblers (mittlerer aerodynamischer Tröpfchen-Durchmesser 4,2 μm) ein Aerosol von 99mTc-Zinnchlorid (450 MBq) in einer Pufferlösung ohne Impfstoff. Die Inhalation wurde mit einer doppelten Maske in einer speziell entwickelten Abzugshaube durchgeführt und das Austreten von Aerosol-Partikeln in die Umwelt gemessen. Die Ganzkörper Verteilung und der regionale C/P-Verteilungskoeffizient (Quotient zentrale über periphere Lungenaktivität) wurden mittels SPECT/CT und Ganzkörper-Szintigraphie bestimmt. Die SPECT-Empfindlichkeit wurde mittels eines Phantoms kalibriert, um die absolute inhalierte Aktivität in der Lunge bestimmen zu können. Ergebnisse: Die Inhalation wurde von allen Studienteilnehmern vollendet und gut vertragen (Peak Flow unverändert, p =0,9). Der Biosicherheitsfilter war frei von Radioaktivität. 1,3±0,6% (0,4–2,6%) der Gesamtaktivität des Verneblers wurde in den Lungen gemessen, mit einem C/P-Verteilungsquotienten von 0,40±0,20 (0,15–1,14). Schlussfolgerung: Die Aufnahme und regionale Verteilung inhalierter Partikel können in einem Aerosol-Impf-Modell mittels radioaktiv markierter Partikel quantitativ bestimmt werden und so zur Optimierung der Parameter beitragen, die für Verteilung und Beladung von aktiven Impfstoff-Partikeln von Bedeutung sind.

Keywords

Aerosol inhalation - pulmonary deposition - SPECT/CT - 99mTc - targeted vaccine delivery - HPV

Schlüsselwörter

Aerosol-Inhalation - Atemwegsabscheidung - SPECT/CT - 99mTc - gezielte Impfstoff-Anwendung - HPV
 

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