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Assessing Lung Inflammation After Nanoparticle Inhalation Using 2-deoxy-2-[18F]fluoro-d-glucose Positron Emission Tomography Imaging

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Abstract

Purpose

The aim of the present study was to evaluate the use of 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) as a noninvasive strategy to assess the time course of inflammatory processes after inhalation of ZnO nanoparticles (NPs) in rats.

Procedures

Healthy, male Sprague–Dawley rats (n = 30) were divided in two groups of 15 animals each. Animals from one group (n = 15) were submitted to ZnO NPs inhalation in a chamber (10 nm to 4 μm particle size; maximum in number concentration, ∼200 nm; concentration = 245 mg/m3). Animals from the other group (n = 15, sham group) were also exposed following the same procedure, but no NPs were introduced into the chamber. Six animals per group were submitted to [18F]FDG-positron emission tomography (PET) studies at days 1, 7, and 28 after exposition, and the [18F]FDG influx constant (K i ) for the lungs was calculated using Patlak graphical analysis and an image derived blood input function. Nine animals per group were killed at 1, 7 and 28 days after exposure (n = 3 per group and time point), and the lungs were harvested and submitted to immunohistochemical and histological analysis.

Results

Significantly higher mean whole-lung K i values were obtained for animals exposed to NPs at days 1 and 7 after exposure (0.0045 ± 0.0016 min−1 and 0.0047 ± 0.0015 min−1, respectively) compared to controls (0.0024 ± 0.0010 min−1 and 0.0019 ± 0.0011 min−1 at 1 and 7 days, respectively). The K i value for exposed animals dropped to 0.0023 ± 0.0010 min−1 at day 28. This value was not significantly different from the values obtained at 1, 7, and 28 days for the control group. Immunofluorescence staining on lung tissue slices from animals exposed to ZnO NPs showed an increase in CD11b reactivity at days 1 and 7, followed by a decrease in CD11b positive cells at 28 days. Hematoxylin–eosin staining showed histological alterations in the exposed lungs to ZnO NPs at days 1 and 7 that recovered at 28 days postexposure.

Conclusions

The [18F]FDG influx rate constant (K i ) could be determined by PET using Patlak analysis and a corrected image derived input function. Higher K i values were obtained for animals exposed to ZnO NPs at days 1 and 7 after exposition. These results were in good concordance with immunohistochemical assays performed on harvested tissue samples.

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References

  1. Blasco C, Picó Y (2011) Determining nanomaterials in food. TrAC 30:84–99

    CAS  Google Scholar 

  2. Zielecka M, Bujnowska E, Kepska B et al (2011) Antimicrobial additives for architectural paints and impregnates. Prog Org Coat 72:193–201

    Article  CAS  Google Scholar 

  3. Blyszko J, Kiernozycki W, Guskos N et al (2008) Study of mechanical properties of concrete with low concentration of magnetic nanoparticles. J Non-Cryst Solids 354:4515–4518

    Article  CAS  Google Scholar 

  4. Stroyuk AL, Shvalagin VV, Kuchmii SY (2005) Photochemical synthesis and optical properties of binary and ternary metal–semiconductor composites based on zinc oxide nanoparticles. J Photochem Photobio A 173:185–194

    Article  CAS  Google Scholar 

  5. Wang MC (2010) Synthesis of zinc oxide nanocrystalline powders for cosmetic applications. Ceram Int 36:693–698

    Article  Google Scholar 

  6. Yukuphanoglu F (2011) Synthesis and electro-optic properties of nanosized-boron doped cadmium oxide thin films for solar cell applications. Sol Energy 85:2704–2709

    Article  Google Scholar 

  7. Sahay R, Sundaramurthy J, Suresh KP et al (2012) Synthesis and characterization of CuO nanofibers, and investigation for its suitability as blocking layer in ZnO nps based dye sensitized solar cell and as photocatalyst in organic dye degradation. J Solid State Chem 186:261–267

    Article  CAS  Google Scholar 

  8. Locatelli E, Gil L, Israel LL et al (2012) Biocompatible nanocomposite for PET/MRI hybrid imaging. Int J Nanomed 7:6021–6033

    CAS  Google Scholar 

  9. Weiss C, Diabate S (2011) A special issue on nanotoxicology. Arch toxicol 85:705–706

    Article  CAS  PubMed  Google Scholar 

  10. Ju-Nam Y, Lead JR (2008) Manufactured nanoparticles: an overview of their chemistry, interactions and potential environmental implications. Sci Total Environ 400:396–414

    Article  CAS  PubMed  Google Scholar 

  11. Handy RD, von der Kammer F, Lead JR et al (2008) The ecotoxicology and chemistry of manufactured nanoparticles. Ecotoxicology 17:287–314

    Article  CAS  PubMed  Google Scholar 

  12. Osmond MJ, McCall MJ (2010) Zinc oxide nanoparticles in modern sunscreens: an analysis of potential exposure and hazard. Nanotoxicology 4:15–41

    Article  CAS  PubMed  Google Scholar 

  13. Sayes CM, Reed KL, Wahrheit DB (2007) Assessing toxicity of fine and nanoparticles: comparing in vitro measurements to in vivo pulmonary toxicity profiles. Toxicol Sci 97:163–180

    Google Scholar 

  14. Cho WS, Duffin R, Poland CA et al (2012) Differential pro-inflammatory effects of metal oxide nanoparticles and their soluble ions in vitro and in vivo; zinc and copper nanoparticles, but not their ions, recruit eosinophils to the lungs. Nanotoxicology 6:22–35

    Google Scholar 

  15. Locke LW, Williams MB, Fairchild KD et al (2011) FDG-PET quantification of lung inflammation with image-derived blood input function in mice. Int J Mol Imaging 22:356730

    Google Scholar 

  16. Chen DL, Bedient TJ, Kozlowski J et al (2009) [18F]Fluorodeoxyglucose positron emission tomography for lung antiinflammatory response evaluation. Am J Respir Crit Care Med 180:533–539

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Martin TR (2010) Neutrophils and lung injury: getting it right. J Clin Invest 110:1603–1605

    Article  Google Scholar 

  18. Zambelli V, Di Grigoli G, Scanziani M et al (2012) Time course of metabolic activity and cellular infiltration in a murine model of acid-induced lung injury. Intens Care Med 38:694–701

    Article  CAS  Google Scholar 

  19. Chen DL, Schuster DP (2004) Positron emission tomography with [18F]fluorodeoxyglucose to evaluate neutrophil kinetics during acute lung injury. Am J Physiol Lung Cell Mol Physiol 286:L834–L840

    Article  CAS  PubMed  Google Scholar 

  20. Jones HA, Clark RJ, Rhodes CG et al (1994) In vivo measurement of neutrophil activity in experimental lung inflammation. Am J Resp Crit Care 149:1635–1639

    Google Scholar 

  21. Jones HA, Sriskandan S, Peters AM et al (1997) Dissociation of neutrophil emigration and metabolic activity in lobar pneumonia and bronchiectasis. Eur Respir J 10:795–803

    CAS  PubMed  Google Scholar 

  22. Schroeder T, Vidal-Melo MF, Musch G et al (2008) Modeling pulmonary kinetics of 2-deoxy-2-[18F]fluoro-D-glucose during acute lung injury. Acad Radiol 15:763–775

    Article  PubMed Central  PubMed  Google Scholar 

  23. Zhou Z, Kozlowski J, Goodrich AL et al (2005) Molecular imaging of lung glucose uptake after endotoxin in mice. Am J Physiol Lung Cell Mol Physiol 289:L760–L768

    Article  CAS  PubMed  Google Scholar 

  24. Hansson L, Ohlsson T, Valind S et al (1999) Glucose utilization in the lungs of septic rats. Eur J Nucl Med 26:1340–1344

    Article  CAS  PubMed  Google Scholar 

  25. Fang YH, Muzic RF Jr (2008) Spillover and partial-volume correction for image-derived input functions for small-animal 18F-FDG PET studies. J Nucl Med 49:606–614

    Article  PubMed  Google Scholar 

  26. van der Weerdt AP, Klein LJ, Boellaard R et al (2001) Image-derived input functions for determination of MRGlu in cardiac 18F-FDG PET scans. J Nucl Med 42:1622–1629

    PubMed  Google Scholar 

  27. Patlak CS, Blasberg RG, Fenstermacher JD (1987) Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. J Cereb Blood Flow Metab 3:1–7

    Article  Google Scholar 

  28. Clausen SK, Bergqvist M, Poulsen LK et al (2003) Development of sensitisation or tolerance following repeated OVA inhalation in BALB/cJ mice. Dose-dependency and modulation by the Al(OH)3 adjuvant. Toxicology 184:51–68

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors would like to thank the 7th Framework Program for funding this work through the HINAMOX PROJECT contract agreement no. NMP4-SL-2009-228825, and QNANO SP4-Capacities-2010-262163 for support. The authors also gratefully acknowledge the support of the Ministerio de Economía y Competitividad (former Ministerio de Ciencia e Innovación) for financial support (CENIT CIN/1559/2009), Professor Ronald F. Ziolo from Centro de Investigación en Química Aplicada (Saltillo, Mexico) for fruitful discussion and Plasmachem GmbH for kindly donating ZnO NPs.

Conflict of Interest

None of the authors have any conflict of interest to disclose.

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Authors and Affiliations

  1. Radiochemistry Department, Molecular Imaging Unit, CIC biomaGUNE, San Sebastian, Spain

    Carlos Pérez-Campaña, Vanessa Gómez-Vallejo, Maria Puigivila & Jordi Llop

  2. Molecular Imaging Unit, CIC biomaGUNE, San Sebastian, Spain

    Abraham Martin

  3. Animal Facility, Molecular Imaging Unit, CIC biomaGUNE, San Sebastian, Spain

    Teresa Calvo-Fernández

  4. Biosurfaces Unit, CIC biomaGUNE, San Sebastian, Spain

    Sergio E. Moya

  5. National Research Centre for the Working Environment, Copenhagen, Denmark

    Søren Thor Larsen

  6. Fundació Pasqual Maragall, Barcelona, Spain

    Juan D. Gispert

Authors
  1. Carlos Pérez-Campaña
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  2. Vanessa Gómez-Vallejo
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  4. Abraham Martin
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  9. Jordi Llop
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Correspondence to Jordi Llop.

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Pérez-Campaña, C., Gómez-Vallejo, V., Puigivila, M. et al. Assessing Lung Inflammation After Nanoparticle Inhalation Using 2-deoxy-2-[18F]fluoro-d-glucose Positron Emission Tomography Imaging. Mol Imaging Biol 16, 264–273 (2014). https://doi.org/10.1007/s11307-013-0682-3

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  • DOI: https://doi.org/10.1007/s11307-013-0682-3

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