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Assessment of Regional Lung Ventilation with Positron Emission Tomography Using the Radiofluorinated Gas [18F]SF6: Application to an Animal Model of Impaired Ventilation

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Abstract

Purpose

Clinical ventilation studies are primarily performed with computerized tomography (CT) and more often with single-photon emission Computerized tomography (SPECT) using radiolabelled aerosols, both presenting certain limitations. Here, we investigate the use of the radiofluorinated gas [18F]SF6 as a positron emission tomography (PET) ventilation marker in an animal model of impaired lung ventilation.

Procedures

Sprague–Dawley rats (n = 15) were randomly assigned to spontaneous ventilation (sham group), endotracheal administration of phosphate-buffered saline (PBS group), or endotracheal administration of lipopolysaccharide (LPS group). PET-[18F]SF6 images (10-min acquisition) were acquired at t = 48 h after LPS or PBS administration under mechanical ventilation. CT images were acquired after each PET session. Volumes of interest were manually delineated in the lungs on CT images, and voxel-by-voxel analysis was carried out on PET images to obtain the corresponding histograms. After the imaging sessions, lungs were harvested to conduct histological analysis.

Results

Ventilation studies in sham animals showed uniform distribution of [18F]SF6 and fast elimination of the radioactivity after discontinuation of the administration. For PBS- and LPS-treated rats, ventilation defects were observed on PET images in some animals, identified as regions with low presence of the radiolabelled gas. Hypoventilated areas co-localized with regions with higher x-ray attenuation than healthy lungs on the CT images, suggesting the presence of oedema and, in some cases, atelectasis. Histograms obtained from PET images showed quasi-Gaussian distributions for control animals, while PBS- and LPS-treated animals demonstrated the presence of hypoventilated voxels. Deviation of the histograms from Gaussian distribution correlated with histological score was obtained by ex vivo histological analysis.

Conclusions

[18F]SF6 is an appropriate marker of regional lung ventilation and may find application in the early diagnose of acute lung disease.

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Funding

The work was supported by MCIN/AEI/10.13039/501100011033 (PDC2021-121497-I00 and PID2020-117656RB-I00) and Instituto de Salud Carlos III (DTS21/00008). This work was performed under the Maria de Maeztu Units of Excellence Programme — Grant MDM-2017–0720 funded by MCIN/AEI/10.13039/501100011033 and RYC-2017–22412.

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Authors and Affiliations

  1. CIC biomaGUNE, Basque Research and Technology Alliance (BRTA), Paseo Miramón 182, 20014, San Sebastian, Guipuzcoa, Spain

    Rossana Passannante, Vanessa Gómez-Vallejo, Unai Cossío, Jesús Ruiz-Cabello, Aitor Lekuona, Victor Salinas & Jordi Llop

  2. Ikerbasque, Basque Foundation for Science, Plaza Euskadi 5, 48009, Bilbao, Spain

    Jesús Ruiz-Cabello & Abraham Martín

  3. Centro de Investigación Biomédica en Red – Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029, Madrid, Spain

    Jesús Ruiz-Cabello, Laura Amado-Rodríguez & Guillermo M. Albaiceta

  4. Departamento de Ciencias Farmacéuticas, Facultad de Farmacia, Universidad Complutense Madrid, Plaza Ramón y Cajal s/n, 28040, Madrid, Spain

    Jesús Ruiz-Cabello

  5. Hospital Universitario Central de Asturias, Unidad de Cuidados Críticos Cardiológicos, 33011, Oviedo, Spain

    Laura Amado-Rodríguez & Guillermo M. Albaiceta

  6. Instituto de Investigación Sanitaria del Principado de Asturias, 33011, Oviedo, Spain

    Laura Amado-Rodríguez & Guillermo M. Albaiceta

  7. Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, 33005, Oviedo, Spain

    Guillermo M. Albaiceta

  8. Laboratory of Neuroimaging and Biomarkers of Inflammation, Achucarro Basque Center for Neuroscience, Science Park UPV/EHU, Sede Building B. Sarriena, 48940, Leioa, Spain

    Abraham Martín

  9. Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia

    Luka Rejc

Authors
  1. Rossana Passannante
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  2. Vanessa Gómez-Vallejo
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  3. Unai Cossío
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  4. Jesús Ruiz-Cabello
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  6. Victor Salinas
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  7. Laura Amado-Rodríguez
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  8. Guillermo M. Albaiceta
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  9. Abraham Martín
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  10. Luka Rejc
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  11. Jordi Llop
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Contributions

J. L., A. M., and L. R. designed the study, interpreted the data, and wrote the manuscript. V. G.-V., A. L., and V. S. performed the radiochemical syntheses. R. P. and U.C. performed the PET-CT experiments. L. A.-R. and G. M. A., performed the ex vivo analysis of tissue samples and contributed to the interpretation of the data and writing of the manuscript. J. R. C. contributed to the interpretation of the images and writing of the manuscript.

Corresponding author

Correspondence to Jordi Llop.

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Conflict of Interest

Jordi Llop, Vanessa Gómez-Vallejo, and Aitor Lekuona are co-inventors of the patent that protects the production process for the radiofluorinated gas (PCT/EP2017/065900) granted in the USA (US10849994B2) and Europe (EP3474902B1). No other potential conflicts of interest relevant to this article exist.

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Passannante, R., Gómez-Vallejo, V., Cossío, U. et al. Assessment of Regional Lung Ventilation with Positron Emission Tomography Using the Radiofluorinated Gas [18F]SF6: Application to an Animal Model of Impaired Ventilation. Mol Imaging Biol 25, 413–422 (2023). https://doi.org/10.1007/s11307-022-01773-7

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