Magnetic iron oxide nanoparticles as MRI contrast agents -- a comprehensive physical and theoretical study

R. Taukulis¹ - M. Widdrat² - M. Kumari³ - D. Heinke⁴ - M. Rumpler⁵ - É. Tompa⁶ - R. Uebe^7,8 - A. Kraupner⁴ - A. Cēbers¹ - D. Schüler^7,8 - M. Pósfai⁶ - A. M. Hirt³ - D. Faivre²

¹ Institute of Physics University of Latvia, 8 Zeļļu, LV-1002 Rīga, Latvia
² Department of Biomaterials, Max Planck Institute of Colloids and Interfaces, Science Park Golm, 14424 Potsdam, Germany
³ Institute of Geophysics, ETH-Zürich, Sonneggstrasse 5, CH-8092 Zürich, Switzerland
⁴ nanoPET Pharma GmbH, Luisencarrée, Robert‐Koch‐Platz 4, 10115 Berlin, Germany
⁵ Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Center Meidling, 1 Medical Department, Hanusch-Krankenhaus, Heinrich Collin Strasse 30, 1140 Vienna, Austria
⁶ Department of Earth and Environmental Sciences, University of Pannonia, Egyetem u. 10, H8200 Veszprém, Hungary
⁷ Ludwig-Maximilians-Universität München, Dept. Biologie I, Mikrobiologie, LMU Biozentrum, Großhaderner Str. 4, D-82152 Planegg Martinsried, Germany
⁸ Universität Bayreuth, Dept. Microbiologie, Universitätssstraße 30, 95447 Bayreuth, Germany

Abstract
Magnetite nanoparticles, especially superparamagnetic iron oxide nanoparticles, are established contrast agents for magnetic resonance imaging. Magnetosomes, which are magnetite nanoparticles of biological origin, have been shown to have better contrast properties than current formulations possibly because of their larger size and high monodispersity. Here, we present an integrated study of magnetosomes and synthetic magnetite nanoparticles of varying size, hence, magnetic properties. We investigate not only the relaxation times as a measure for the contrast properties of these particles, but also their cytotoxicity and demonstrate the higher contrast of the larger particles. A theoretical model is presented that enables us to simulate the R₂/R₁ ratio of a contrast agent and confirm that larger particles offer higher contrast. The results from this study illustrate the possibility to obtain colloidal stability of large magnetic nanoparticles for magnetic resonance imaging applications and serve as an impetus for a more quantitative description of the contrast effect as a function of the size. Tables 3, Figs 20, Refs 52.