Lumazine Synthase Protein Nanoparticle-Gd(III)-DOTA Conjugate as a T-1 contrast agent for high-field MRI

作者:Song YoungKyu; Kang Young Ji; Jung Hoesu; Kim Hansol; Kang Sebyung; Cho HyungJoon
来源:Scientific Reports, 2015, 5(1): 15656.
DOI:10.1038/srep15656

摘要

<jats:title>Abstract</jats:title><jats:p>With the applications of magnetic resonance imaging (MRI) at higher magnetic fields increasing, there is demand for MRI contrast agents with improved relaxivity at higher magnetic fields. Macromolecule-based contrast agents, such as protein-based ones, are known to yield significantly higher <jats:italic>r</jats:italic><jats:sub><jats:italic>1</jats:italic></jats:sub> relaxivity at low fields, but tend to lose this merit when used as <jats:italic>T</jats:italic><jats:sub>1</jats:sub> contrast agents (<jats:italic>r</jats:italic><jats:sub>1</jats:sub><jats:italic>/r</jats:italic><jats:sub>2</jats:sub> = 0.5 ~ 1), with their <jats:italic>r</jats:italic><jats:sub>1</jats:sub> decreasing and <jats:italic>r</jats:italic><jats:sub>2</jats:sub> increasing as magnetic field strength increases. Here, we developed and characterized an <jats:italic>in vivo</jats:italic> applicable magnetic resonance (MR) positive contrast agent by conjugating Gd(III)-chelating agent complexes to lumazine synthase isolated from <jats:italic>Aquifex aeolicus</jats:italic> (AaLS). The <jats:italic>r</jats:italic><jats:sub><jats:italic>1</jats:italic></jats:sub> relaxivity of Gd(III)-DOTA-AaLS-R108C was 16.49 mM<jats:sup>−1</jats:sup>s<jats:sup>−1</jats:sup> and its <jats:italic>r</jats:italic><jats:sub>1</jats:sub><jats:italic>/r</jats:italic><jats:sub>2</jats:sub> ratio was 0.52 at the magnetic field strength of 7 T. The results of 3D MR angiography demonstrated the feasibility of vasculature imaging within 2 h of intravenous injection of the agent and a significant reduction in <jats:italic>T</jats:italic><jats:sub>1</jats:sub> values were observed in the tumor region 7 h post-injection in the SCC-7 flank tumor model. Our findings suggest that Gd(III)-DOTA-AaLS-R108C could serve as a potential theranostic nanoplatform at high magnetic field strength.</jats:p>

  • 出版日期2015-10-23