Nanoparticle contrast-enhanced micro-CT: A preclinical tool for the 3D imaging of liver and spleen in longitudinal mouse studies
| Autor: | Cedo M. Bagi, Jeffrey Morin, Melba G. Dokmanovich, Balasubramanian Manickam, Richard Goldstein, Crystal T. Bluette, Chang-Ning Liu |
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| Rok vydání: | 2018 |
| Předmět: |
Male
Pathology medicine.medical_specialty Kupffer Cells Phagocytosis Contrast Media Spleen Gadolinium 030204 cardiovascular system & hematology Toxicology Kidney 030226 pharmacology & pharmacy 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Imaging Three-Dimensional Medicine Distribution (pharmacology) Animals Longitudinal Studies Pharmacology business.industry Kupffer cell Soft tissue Mononuclear phagocyte system X-Ray Microtomography Image Enhancement Mice Inbred C57BL medicine.anatomical_structure chemistry Liver Nanoparticles business Toxicant |
| Zdroj: | Journal of pharmacological and toxicological methods. 96 |
| ISSN: | 1873-488X |
| Popis: | In drug discovery and development, X-ray micro-computed tomography (micro-CT) has gained increasing importance over the past decades. In recent years, micro-CT imaging of soft tissues has become popular due to the introduction of a variety of radiopaque contrast agents. More recently, nanoparticle-based ExiTron nano 12,000 has become commercially available for the nonclinical micro-CT imaging of soft tissues in rodents. Phagocytosis and accumulation of the contrast agent by Kupffer cells in the liver, as well as macrophages in the spleen, increase the soft tissue X-ray attenuation for up to 6 months. Therefore, it is essential to understand the potential toxicity of this nanomaterial in micro-CT imaging prior to its application in pharmacology and/or toxicology studies. Herein, we describe the time-course and distribution of the contrast in the liver, spleen and blood after a single intravenous injection (IV) of this nanoparticle contrast agent at 0.1 ml/mouse. Thoracic images of male adult C57BL/6 mice were acquired using a Bruker SkyScan 1276 micro-CT over a period of 29 days. The stability of X-ray attenuation enhancement in the above tissues was also tested after a single dose of Kupffer cell toxicant gadolinium chloride (GdCl3) at 15 mg/kg on day 2. The liver, spleen and kidney were examined microscopically on days 15 and 29 post treatment. Serum and liver cytokines (IL-1β, IL-2, IL-6, IL-10, IL-12p70, IFN-γ, IP-10, MIP1-α, MIP1-β and TNF-α) were quantified on days 15 and 29 as indicators of a pro-inflammatory response to treatment. This study determined that there was an accumulation of amphophilic granular material in the cells of the mononuclear phagocyte system in the liver and spleen following a single dose of ExiTron nano 12,000 and a second dose of GdCl3 or its vehicle. However, ExiTron nano12000 contrast administration did not cause any hepatotoxicity in the liver, nor did pro-inflammatory cytokines release in the liver or serum. Similarly, there were no adverse pathologies in the spleen or kidneys. In summary, ExiTron nano12000 contrast agent-enhanced micro-CT could be used as a safe method in up to 29-day longitudinal efficacy and toxicology mouse studies for the non-invasive assessment of the liver and spleen. |
| Databáze: | OpenAIRE |
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