title: Gold nanoparticles allow detection of early-stage edema in mice via computed tomography imaging.
abstract: Due to their high X-ray attenuation, gold nanoparticles (GNPs) emerged as preclinical contrast agents by giving high vasculature contrast. For this reason, GNPs are regularly applied for computed tomography (CT) imaging of tumors but not for the visualization of inflammation. The aim of this study was to evaluate the biocompatibility and applicability of preclinical GNPs (AuroVist™) of two different sizes (1.9 nm and 15 nm) for the detection of inflammation-associated phagocytes in early-stage edema. Both GNP variants were stable under in vitro conditions and achieved high micro-CT (mCT) contrast after embedment into agarose. Fifteen-nanometer GNPs were detected after uptake into macrophages via mCT imaging exhibiting higher X-ray contrast than cells treated with 1.9 nm GNPs and untreated ones. Both 1.9 nm and 15 nm GNPs exhibited good biocompatibility on murine macrophages according to ATP and cellular dehydrogenase levels. Reactive oxygen species levels produced by phagocytic cells decreased significantly (P≤0.05) after co-incubation with GNPs regardless of the size of the nanoparticle (NP) in comparison to untreated control cells. In vivo mCT studies of inflammation imaging revealed that GNPs with a diameter of 15 nm accumulated within subcutaneous edema 2 hours after injection with a maximum signaling 8 hours postinjection and could be detected up to 48 hours within the edema region. In contrast, 1.9 nm GNPs were not shown to accumulate at the site of the inflammation region and were mostly excreted via the renal system 2-4 hours after injection. In conclusion, our study demonstrated that both GNP variants (1.9 nm and 15 nm) were stable and biocompatible under in vitro conditions. However, only 15 nm NPs have the potential as contrast agent for phagocyte labeling and applications in CT imaging of inflammation on a cellular level.
authors.affiliation: Institute of Diagnostic and Interventional Radiology, University Hospital Jena, Jena, Germany.
authors.forename: Jenny
authors.initials: J
authors.lastname: Domey
authors.affiliation: Institute of Diagnostic and Interventional Radiology, University Hospital Jena, Jena, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Teichgräber
authors.affiliation: Institute of Diagnostic and Interventional Radiology, University Hospital Jena, Jena, Germany.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Hilger
mesh_terms: D000818:Animals; D002460:Cell Line / Q000187:drug effects; D003287:Contrast Media; D004487:Edema / Q000175:diagnosis*; D006046:Gold; D007249:Inflammation / Q000473:pathology*; D008264:Macrophages / Q000187:drug effects; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry; D051379:Mice; D008815:Mice, Inbred Strains; D010316:Particle Size; D010586:Phagocytes / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014057:Tomography, X-Ray Computed / Q000379:methods*
chemical_list: D003287:Contrast Media; D017382:Reactive Oxygen Species; D006046:Gold
keywords: AuroVist™; GNP; biocompatibility; inflammation; phagocytes