Functionalized Gold Nanoparticles as Contrast Agents for Proton and Dual Proton/Fluorine MRI

Abstract

Gold nanoparticles carrying fluorinated ligands in their monolayer are, by themselves, contrast agents for ¹⁹F magnetic resonance imaging displaying high sensitivity because of the high density of fluorine nuclei achievable by grafting suitable ligands on the gold core surface. Functionalization of these nanoparticles with Gd(III) chelates allows adding a further functional activity to these systems, developing materials also acting as contrast agents for proton magnetic resonance imaging. These dual mode contrast agents may allow capitalizing on the benefits of ¹H and ¹⁹F magnetic resonance imaging in a single diagnostic session. In this work, we describe a proof of principle of this approach by studying these nanoparticles in a high field preclinical scanner. The Gd(III) centers within the nanoparticles monolayer shorten considerably the ¹⁹F T1 of the ligands but, nevertheless, these systems display strong and sharp NMR signals which allow recording good quality ¹⁹F MRI phantom images at nanoparticle concentration of 20 mg/mL after proper adjustment of the imaging sequence. The Gd(III) centers also influence the T1 relaxation time of the water protons and high quality ¹H MRI images could be obtained. Gold nanoparticles protected by hydrogenated ligands and decorated with Gd(III) chelates are reported for comparison as ¹H MRI contrast agents.

Keywords: 19F MRI; contrast agents; fluorinated monolayers; fluorine; gadolinium; hybrid organic-inorganic nanoparticles; magnetic resonance imaging.

Scheme 1

Structure of thiolated ligands used in this study to prepare gadolinium-functionalized nanoparticles.

Figure 1

¹H NMR spectra of (a) NP-C8TEG/C8-DO3AGd-a in D₂O (500 MHz) and (b) NP-C8TEG in CDCl₃ at 500 MHz.

Figure 2

Characterization of NP-C6OF-PEG. Panel (a) UV-Vis spectrum in CHCl₃ of the nanoparticles; panels (b,c) representative TEM image and histogram of the size dispersion; panels (d,e) ¹⁹F NMR (CD₃OD, 470 MHz) and ¹H NMR (CD₃OD, 500 MHz) spectra, respectively.

Figure 3

(a) ¹⁹F NMR (470 MHz, CD₃OD) of NP-C6OF-PEG and (b) of NP-C6OF-PEG/C6OF-DO3AGd.

Figure 4

¹⁹F MRI Phantom experiments run on solutions of: upper panels, NP-C6OF-PEG at (A): 40 mg/mL; (B): 20 mg/mL; (C): 10 mg/mL; lower panels, NP-C6OF-PEG/C6OF-DO3AGd at (D): 40 mg/mL; (E): 20 mg/mL; (F): 10 mg/mL.

Figure 5

7 T ¹H MRI images obtained in phantom experiments on solutions of nanoparticles NP-C6OF-PEG/C6OF-DO3AGd (A); NP-C6OF-PEG (B); NP-C8TEG/C8-DO3AGd-a (C); NP-C8TEG/C8-DO3AGd-b (D). All experiments were performed on 40 mg/mL solutions of the nanoparticles.