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Transferrin-Coated Gadolinium Nanoparticles as MRI Contrast Agent
Authors:Huedayi Korkusuz  Karsten Ulbrich  Katerina Welzel  Verena Koeberle  Waralee Watcharin  Ute Bahr  Valery Chernikov  Thomas Knobloch  Sabine Petersen  Frank Huebner  Hanns Ackermann  Svetlana Gelperina  Wolfgang Kromen  Renate Hammerstingl  Joerg Haupenthal  Frank Gruenwald  Jens Fiehler  Stefan Zeuzem  Joerg Kreuter  Thomas J Vogl  Albrecht Piiper
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
10. Department of Diagnostic and Interventional Radiology, Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, 60590, 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
9. Helmholtz Institute for Pharmaceutical Research Saarland, Department of Drug Design and Optimization, University of Saarland, 66123, Saarbrücken, Germany
8. Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Martinistra?e 52, 20246, Hamburg, Germany
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.
Keywords:
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