title: Comparison of small animal CT contrast agents.
abstract: Non-invasive in vivo small animal computed tomography (CT) imaging provides high resolution bone scans but cannot differentiate between soft tissues. For most applications injections of contrast agents (CAs) are necessary. Aim of this study was to uncover the advantages and disadvantages of commercially available CT CAs (ExiTron nano 12 000 and 6000, eXIA 160 and 160XL, Fenestra VC and LC) regarding their pharmacokinetics, toxicological side-effects and the influence of anesthesia on the biodistribution, based on an injection volume of 100 μL/25 g body weight. The pharmacokinetics of the CAs were determined for up to five days. The CA-induced toxicological/physiological side-effects were evaluated by determining blood counts, liver enzymes, thyroxine and total protein values, pro-inflammatory mediators (messenger ribonucleic acid (mRNA)), histology and immunohistochemistry. ExiTron nano 12 000 and 6000 yielded a long-term contrast enhancement (CE) in the liver and spleen for up to five days. Some of the evaluated CAs did not show any CE at all. Anesthesia did not impair the CAs' biodistribution. The CAs differentially affected the body weight, blood counts, liver enzymes, thyroxine and total protein values. ExiTron nano 12 000 and 6000 induced histiocytes in the liver and spleen. Moreover, ExiTron nano 12 000 and eXIA 160 enhanced tumor necrosis factor (TNF) mRNA expression levels in the kidneys. Thus, we recommend ExiTron nano 12 000 and 6000 when multiple injections should be avoided. We recommend careful selection of the employed CA in order to achieve an acceptable CE in the organs of interest and to avoid influences on the animal physiology. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tuebingen, Tuebingen, Germany.
authors.forename: Julia G
authors.initials: JG
authors.lastname: Mannheim
authors.affiliation: Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tuebingen, Tuebingen, Germany.|Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schlichthaerle
authors.affiliation: Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tuebingen, Tuebingen, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Kuebler
authors.affiliation: Institute of Pathology, University Hospital Tuebingen, Eberhard Karls University Tuebingen, Tuebingen, Germany.
authors.forename: Leticia
authors.initials: L
authors.lastname: Quintanilla-Martinez
authors.affiliation: Institute of Pathology, University Hospital Tuebingen, Eberhard Karls University Tuebingen, Tuebingen, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Kohlhofer
authors.affiliation: Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tuebingen, Tuebingen, Germany.|Department of Dermatology, Eberhard Karls University Tuebingen, Tuebingen, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Kneilling
authors.affiliation: Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tuebingen, Tuebingen, Germany.
authors.forename: Bernd J
authors.initials: BJ
authors.lastname: Pichler
mesh_terms: D000758:Anesthesia; D000818:Animals; D003287:Contrast Media / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000633:toxicity; D004347:Drug Interactions; D006352:Heart Ventricles / Q000000981:diagnostic imaging; D006644:Histiocytes / Q000187:drug effects; D007668:Kidney / Q000000981:diagnostic imaging; D008099:Liver / Q000000981:diagnostic imaging / Q000473:pathology; D051379:Mice; D009132:Muscles / Q000000981:diagnostic imaging; D013154:Spleen / Q000000981:diagnostic imaging / Q000473:pathology; D014057:Tomography, X-Ray Computed; D055114:X-Ray Microtomography / Q000379:methods*
chemical_list: D003287:Contrast Media
keywords: biodistribution; contrast agents; pharmacokinetics; side-effects; small animal CT