Molecular Imaging and Biology, April, 2013, Vol.15(2), p.148(7)
Byline: Huedayi Korkusuz (1), Karsten Ulbrich (2), Katerina Welzel (10), Verena Koeberle (3), Waralee Watcharin (2), Ute Bahr (4), Valery Chernikov (5), Thomas Knobloch (2), Sabine Petersen (10), Frank Huebner (10), Hanns Ackermann (6), Svetlana Gelperina (7), Wolfgang Kromen (10), Renate Hammerstingl (10), Joerg Haupenthal (3,9), Frank Gruenwald (1), Jens Fiehler (8), Stefan Zeuzem (3), Joerg Kreuter (2), Thomas J. Vogl (10), Albrecht Piiper (3) Keywords: Contrast agent; Nanoparticles; Gd-DTPA-human serum albumin-transferrin; Biodistribution; Human serum albumin Abstract: Purpose In this study, the contrasting properties of human serum albumin nanoparticles (HSA-NPs) loaded with gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) and coated with transferrin in MRI in mice are evaluated. Procedures HSA-NPs were conjugated with Gd-DTPA (Gd-HSA-NPs) and coupled with transferrin (Gd-HSA-NP-Tf). Mice underwent MRI before or after injection of Gd-DTPA, Gd-HSA-NP, or Gd-HSA-NP-Tf. Results All the studied contrast agents provided a contrast enhancement (CE) in the blood, heart muscle, and liver. Compared to Gd-DTPA, CE with HSA-NP was achieved at lower Gd doses. Gd-HSA-NP-Tf yielded significantly higher CE than Gd-HSA-NP in the skeletal muscle, blood, cardiac muscle, and liver (p〈0.05). Gd-HSA-NP-Tf achieved a significantly higher CE than Gd-HSA-NP and Gd-DTPA in the blood, cardiac muscle, and liver (p〈0.05). In the brain, only Gd-HSA-NP-Tf was found to cause a significant CE (p〈0.05). Conclusions The Gd-HSA nanoparticles have potential as MRI contrast agents. In particular, Gd-HSA-NP-Tf has a potential as a specific contrast agent for the brain, while the blood--brain barrier is still intact, as well as in the heart, liver, and skeletal muscle. Author Affiliation: (1) Department of Nuclear Medicine, Johann Wolfgang Goethe University Hospital, Theodor-Stern-Kai 7, 60590, Frankfurt/Main, Germany (2) Institute of Pharmaceutical Technology, Biocenter of Johann Wolfgang Goethe University, Max-von-Laue -Str. 9, 60438, Frankfurt, Germany (3) Department of Medicine I, Johann Wolfgang Goethe University Hospital, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany (4) Institute of Pharmaceutical Chemistry, Johann Wolfgang Goethe University, Max-von-Laue-Str. 9, 60438, Frankfurt, Germany (5) Institute of Human Morphology, Russian Academy of Medical Sciences, Zurupa st. 3, 117418, Moscow, Russia (6) Department of Biomathematics, Johann Wolfgang Goethe University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany (7) Nanosystem Ltd, 7-th Kozhuhovskaya st., 20, 115193, Moscow, Russia (8) Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany (9) Helmholtz Institute for Pharmaceutical Research Saarland, Department of Drug Design and Optimization, University of Saarland, 66123, Saarbrucken, Germany (10) Department of Diagnostic and Interventional Radiology, Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany Article History: Registration Date: 06/07/2012 Online Date: 19/07/2012 Article note: Karsten Ulbrich, Katerina Welzel, and Verena Koeberle contributed equally to this work. Joerg Kreuter, Thomas J. Vogl, and Albrecht Piiper shared senior authorship.
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