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Therefore, we have studied the deposition patterns of inhaled 20 nm gold nanoparticles (AuNP) in 7\u221290 day old rats and their biokinetics in 60 day old ones. Wistar\u2212Kyoto rats inhaled intratracheally 20 nm 195Au-radiolabeled AuNP by negative pressure ventilation over 2 h. Immediately afterward lungs were excised, inflated and microwave dried. AuNP deposition was analyzed by single-photon emission computed tomography, computed-tomography and autoradiography. Completely balanced, quantitative biodistributions in major organs and all body tissues and total excretion were analyzed from 1 h to 28 d after inhalation. Intratracheal inhalation caused AuNP deposition predominately in the caudal lungs, independent of age. About 30% AuNP were deposited on airway epithelia and rapidly cleared by mucociliary clearance. About 80% of AuNP deposited in alveoli was relocated from the epithelium into the interstitium within 24 h and was inaccessible to broncho-alveolar lavage. During interstitial long-term retention, re-entrainment within macrophages back onto the lung epithelium and to the larynx and gastrointestinal tract (GIT) dominated AuNP clearance (rate 0.03 d\u22121) In contrast, AuNP-translocation across the air\u2212blood barrier was much smaller leading to persistent retention in secondary organs and tissues in the ranking order liver &amp;gt; soft issue &amp;gt; spleen &amp;gt; kidneys &amp;gt; skeleton &amp;gt; blood &amp;gt; uterus &amp;gt; heart &amp;gt; brain. The age-independent, inhomogeneous AuNP deposition was probably caused by the negative pressure ventilation. Long-term AuNP clearance was dominated by macrophage-mediated transport from the interstitium to the larynx and GIT. Translocation across the rat air\u2212blood barrier appeared to be similar to that of humans for similar sized AuNP.<\/jats:p>","DOI":"10.1021\/acsnano.8b01826","type":"journal-article","created":{"date-parts":[[2018,8,7]],"date-time":"2018-08-07T15:14:38Z","timestamp":1533654878000},"page":"7771-7790","source":"Crossref","is-referenced-by-count":87,"title":["Age-Dependent\nRat Lung Deposition Patterns of Inhaled\n20 Nanometer Gold Nanoparticles and their Quantitative Biokinetics\nin Adult Rats"],"prefix":"10.1021","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0702-6567","authenticated-orcid":true,"given":"Wolfgang G.","family":"Kreyling","sequence":"first","affiliation":[{"name":"Helmholtz Zentrum Mu\u0308nchen\u2500German Research Center for Environmental Health , , Ingolstaedter Landstrasse 1 , ,","place":["Neuherberg\/Munich, Germany, D-85764"]},{"name":"Helmholtz Center Munich\u2500German Research Center for Environmental Health , , Ingolstaedter Landstrasse 1 , ,","place":["Neuherberg\/Munich, Germany, D-85764"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winfried","family":"Mo\u0308ller","sequence":"additional","affiliation":[{"name":"Helmholtz Zentrum Mu\u0308nchen\u2500German Research Center for Environmental Health , , Ingolstaedter Landstrasse 1 , ,","place":["Neuherberg\/Munich, Germany, D-85764"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Holzwarth","sequence":"additional","affiliation":[{"name":"Joint Research Centre, European Commission , , Via E. Fermi 2749 , , ,","place":["Ispra, Varese, Italy, I-21027"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Hirn","sequence":"additional","affiliation":[{"name":"Helmholtz Zentrum Mu\u0308nchen\u2500German Research Center for Environmental Health , , Ingolstaedter Landstrasse 1 , ,","place":["Neuherberg\/Munich, Germany, D-85764"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Wenk","sequence":"additional","affiliation":[{"name":"Helmholtz Zentrum Mu\u0308nchen\u2500German Research Center for Environmental Health , , Ingolstaedter Landstrasse 1 , ,","place":["Neuherberg\/Munich, Germany, D-85764"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Schleh","sequence":"additional","affiliation":[{"name":"Helmholtz Zentrum Mu\u0308nchen\u2500German Research Center for Environmental Health , , Ingolstaedter Landstrasse 1 , ,","place":["Neuherberg\/Munich, Germany, D-85764"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Scha\u0308ffler","sequence":"additional","affiliation":[{"name":"Helmholtz Zentrum Mu\u0308nchen\u2500German Research Center for Environmental Health , , Ingolstaedter Landstrasse 1 , ,","place":["Neuherberg\/Munich, Germany, D-85764"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Haberl","sequence":"additional","affiliation":[{"name":"Helmholtz Zentrum Mu\u0308nchen\u2500German Research Center for Environmental Health , , Ingolstaedter Landstrasse 1 , ,","place":["Neuherberg\/Munich, Germany, D-85764"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Gibson","sequence":"additional","affiliation":[{"name":"Joint Research Centre, European Commission , , Via E. 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Toxicol."},{"key":"2026090404244489200_cit6","doi-asserted-by":"publisher","first-page":"1647","DOI":"10.1039\/C0CS00018C","article-title":"Biodistribution and Toxicity of Engineered\nGold Nanoparticles:\nA Review of in Vitro and in Vivo Studies","volume":"40","author":"Khlebtsov","year":"2011","journal-title":"Chem. Soc. Rev."},{"key":"2026090404244489200_cit7","doi-asserted-by":"publisher","first-page":"837","DOI":"10.3109\/10408444.2015.1058747","article-title":"Nanomaterial\nTranslocation\u2013the Biokinetics, Tissue Accumulation, Toxicity\nand Fate of Materials in Secondary Organs\u2013a Review","volume":"45","author":"Kermanizadeh","year":"2015","journal-title":"Crit. Rev. 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J. Pharm.\nBiopharm."},{"key":"2026090404244489200_cit23","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1038\/mi.2008.36","article-title":"Differentiation\nand Heterogeneity in the Mononuclear Phagocyte System","volume":"1","author":"Hume","year":"2008","journal-title":"Mucosal Immunol."},{"key":"2026090404244489200_cit24","doi-asserted-by":"publisher","first-page":"815","DOI":"10.2217\/nnm.11.79","article-title":"In Vivo Biodistribution of Nanoparticles","volume":"6","author":"Almeida","year":"2011","journal-title":"Nanomedicine\n(London, U. K.)"},{"key":"2026090404244489200_cit25","doi-asserted-by":"publisher","first-page":"1663","DOI":"10.1016\/j.nano.2016.02.019","article-title":"Ultrasmall\nInorganic Nanoparticles: State-of-the-Art and Perspectives for Biomedical\nApplications","volume":"12","author":"Zarschler","year":"2016","journal-title":"Nanomedicine (N. Y., NY, U. 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Physiol."},{"key":"2026090404244489200_cit33","doi-asserted-by":"publisher","first-page":"L1082","DOI":"10.1152\/ajplung.00325.2016","article-title":"The Total Number\nof Acini Remains Constant Throughout\nPostnatal Rat Lung Development","volume":"311","author":"Barre\u0301","year":"2016","journal-title":"Am.J. Physiol.-Lung\nCell. Mol. Physiol."},{"key":"2026090404244489200_cit34","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.ejps.2017.09.033","article-title":"One (Sub-)Acinus\nfor\nAll: Fate of Inhaled Aerosols in Heterogeneous Pulmonary Acinar Structures","volume":"113","author":"Hofemeier","year":"2018","journal-title":"Eur. J. Pharm. Sci."},{"key":"2026090404244489200_cit35","first-page":"A4440","article-title":"Computational Model\nof a Breathing Lung Illustrates the Influence of the Acinar Structures\non Gas Washout","volume":"195","author":"Schittny","year":"2017","journal-title":"Am. J. Respir. Crit. 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Physiol."},{"key":"2026090404244489200_cit37","first-page":"177","article-title":"Regional Ventilation\nDistribution","volume-title":"Gas Mixing and Distribution\nin the Lung","author":"Hughes","year":"1985"},{"key":"2026090404244489200_cit38","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/B978-0-12-404577-4.00027-8","article-title":"Deposition\nof Particles","volume-title":"Comparative Biology of the\nNormal Lung","author":"Brown","year":"2015"},{"key":"2026090404244489200_cit39","unstructured":"Multiple-Path Particle Dosimetry Model (MPPD Version 3.0); ARA, 2009."},{"key":"2026090404244489200_cit40","first-page":"1","article-title":"Human Respiratory Tract Model for Radiological Protection.\nA Report\nof a Task Group of the International Commission on Radiological Protection","volume":"24","year":"1994","journal-title":"Ann. 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Aerosol Med."},{"key":"2026090404244489200_cit44","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1289\/ehp.929717","article-title":"Pulmonary\nand Thoracic Macrophage Subpopulations and Clearance of Particles\nfrom the Lung","volume":"97","author":"Lehnert","year":"1992","journal-title":"Environ. Health Perspect."},{"key":"2026090404244489200_cit45","first-page":"430","article-title":"Adaptive Responses\nof the Pulmonary Macrophagic System\nto Carbon. II. Morphologic Studies","volume":"38","author":"Adamson","year":"1978","journal-title":"Lab. Invest."},{"key":"2026090404244489200_cit46","doi-asserted-by":"publisher","first-page":"165","DOI":"10.3109\/01902148109052312","article-title":"Dose Response of\nthe Pulmonary Macrophagic System to\nVarious Particulates and Its Relationship to Transepithelial Passage\nof Free Particles","volume":"2","author":"Adamson","year":"1981","journal-title":"Exp. Lung Res."},{"key":"2026090404244489200_cit47","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1002\/path.1711430206","article-title":"Pathways of Cellular\nEfflux and Particulate Clearance\nafter Carbon Instillation to the Lung","volume":"143","author":"Bowden","year":"1984","journal-title":"J. Pathol."},{"key":"2026090404244489200_cit48","doi-asserted-by":"publisher","first-page":"11778","DOI":"10.1021\/nn505399e","article-title":"Critical Determinants\nof Uptake and Translocation of Nanoparticles by the Human Pulmonary\nAlveolar Epithelium","volume":"8","author":"Thorley","year":"2014","journal-title":"ACS Nano"},{"key":"2026090404244489200_cit49","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.1289\/ehp.8006","article-title":"Ultrafine\nParticles Cross Cellular Membranes by Nonphagocytic Mechanisms\nin Lungs and in Cultured Cells. 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