Stable gadolinium based nanoscale lyophilized injection for enhanced MR angiography with efficient renal clearance

Biomaterials. 2018 Mar:158:74-85. doi: 10.1016/j.biomaterials.2017.12.023. Epub 2017 Dec 28.

Abstract

There is a great demand to develop high-relaxivity nanoscale contrast agents for magnetic resonance (MR) angiography with high resolution. However, there should be more focus on stability, ion leakage and excretion pathway of the intravenously injected nanoparticles, which are closely related to their clinic potentials. Herein, uniform ultrasmall-sized NaGdF4 nanocrystal (sub-10 nm) was synthesized using a facile high temperature organic solution method, and the nanocrystals were modified by a ligand-exchange approach using PEG-PAA di-block copolymer. The PEG-PAA modified NaGdF4 nanocrystal (denoted as ppNaGdF4 nanocrystal) exhibited a high r1 relaxivity which was twice of commercially used gadopentetate dimeglumine (Gd-DTPA) injection. MR angiography on rabbit using ppNaGdF4 nanocrystal at a low dose showed enhanced vascular details and long circulation time. Lyophilized powder of ppNaGdF4 nanocrystals have been successfully prepared without aggregation or reduction of MR performance, indicating the stability and an effective way to store this nanoscale contrast agent. No haemolysis was induced by ppNaGdF4 nanocrystal, and an extremely low leakage of gadolinium ions was confirmed. Furthermore, efficient renal excretion was one of the clearance pathways of ppNaGdF4 nanocrystal according to both the time dependent distribution data in blood and tissues and MR images. The in vivo toxicity evaluation further validated the great potential as a clinical agent for blood pool imaging.

Keywords: Compatibility; Contrast agent; Gadolinium based nanocrystals; Lyophilized powder injection; Magnetic resonance angiography.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Contrast Media* / chemistry
  • Gadolinium* / administration & dosage
  • Gadolinium* / chemistry
  • Humans
  • Kidney / diagnostic imaging
  • Kidney / metabolism
  • Magnetic Resonance Angiography / methods*
  • Materials Testing
  • Nanoparticles* / chemistry
  • Rabbits

Substances

  • Contrast Media
  • Gadolinium