Albumin-based nanoparticles as contrast medium for MRI: vascular imaging, tissue and cell interactions, and pharmacokine
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ORIGINAL PAPER
Albumin‑based nanoparticles as contrast medium for MRI: vascular imaging, tissue and cell interactions, and pharmacokinetics of second‑generation nanoparticles E. A. Wallnöfer1 · G. C. Thurner1,5 · C. Kremser1 · H. Talasz2 · M. M. Stollenwerk3,5 · A. Helbok4 · N. Klammsteiner5 · K. Albrecht‑Schgoer6,7 · H. Dietrich8 · W. Jaschke1 · P. Debbage5 Accepted: 31 August 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract This multidisciplinary study examined the pharmacokinetics of nanoparticles based on albumin-DTPA-gadolinium chelates, testing the hypothesis that these nanoparticles create a stronger vessel signal than conventional gadolinium-based contrast agents and exploring if they are safe for clinical use. Nanoparticles based on human serum albumin, bearing gadolinium and designed for use in magnetic resonance imaging, were used to generate magnet resonance images (MRI) of the vascular system in rats (“blood pool imaging”). At the low nanoparticle doses used for radionuclide imaging, nanoparticle-associated metals were cleared from the blood into the liver during the first 4 h after nanoparticle application. At the higher doses required for MRI, the liver became saturated and kidney and spleen acted as additional sinks for the metals, and accounted for most processing of the nanoparticles. The multiple components of the nanoparticles were cleared independently of one another. Albumin was detected in liver, spleen, and kidneys for up to 2 days after intravenous injection. Gadolinium was retained in the liver, kidneys, and spleen in significant concentrations for much longer. Gadolinium was present as significant fractions of initial dose for longer than 2 weeks after application, and gadolinium clearance was only complete after 6 weeks. Our analysis could not account quantitatively for the full dose of gadolinium that was applied, but numerous organs were found to contain gadolinium in the collagen of their connective tissues. Multiple lines of evidence indicated intracellular processing opening the DTPA chelates and leading to gadolinium longterm storage, in particular inside lysosomes. Turnover of the stored gadolinium was found to occur in soluble form in the kidneys, the liver, and the colon for up to 3 weeks after application. Gadolinium overload poses a significant hazard due to the high toxicity of free gadolinium ions. We discuss the relevance of our findings to gadolinium-deposition diseases. Keywords Albumin nanoparticles · MRI contrast medium gadolinium · Pharmacokinetics · Radiolabeling · Immunohistochemistry · Quantitative chemical analysis Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00418-020-01919-0) contains supplementary material, which is available to authorized users. * P. Debbage Paul.Debbage@i‑med.ac.at 1
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Division of Histology and Embryology, Department of Anatomy, Histology and Embryology, Medical University of Innsbruck, Müllerstrasse 59, 6020 Innsbruck, Austria
Department of Radiology,
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