Pre-clinical dose-ranging efficacy, pharmacokinetics, tissue biodistribution, and toxicity of a targeted contrast agent for MRI of amyloid deposition in Alzheimer's disease

Sci Rep. 2020 Sep 30;10(1):16185. doi: 10.1038/s41598-020-73233-7.


In these preclinical studies, we describe ADx-001, an Aβ-targeted liposomal macrocyclic gadolinium (Gd) imaging agent, for MRI of amyloid plaques. The targeting moiety is a novel lipid-PEG conjugated styryl-pyrimidine. An MRI-based contrast agent such as ADx-001 is attractive because of the lack of radioactivity, ease of distribution, long shelf life, and the prevalence of MRI scanners. Dose-ranging efficacy studies were performed on a 1 T MRI scanner using a transgenic APP/PSEN1 mouse model of Alzheimer's disease. ADx-001 was tested at 0.10, 0.15, and 0.20 mmol Gd/kg. Gold standard post-mortem amyloid immunostaining was used for the determination of sensitivity and specificity. ADx-001 toxicity was evaluated in rats and monkeys at doses up to 0.30 mmol Gd/kg. ADx-001 pharmacokinetics were determined in monkeys and its tissue distribution was evaluated in rats. ADx-001-enhanced MRI demonstrated significantly higher (p < 0.05) brain signal enhancement in transgenic mice relative to wild type mice at all dose levels. ADx-001 demonstrated high sensitivity at 0.20 and 0.15 mmol Gd/kg and excellent specificity at all dose levels for in vivo imaging of β amyloid plaques. ADx-001 was well tolerated in rats and monkeys and exhibited the slow clearance from circulation and tissue biodistribution typical of PEGylated nanoparticles.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / diagnostic imaging*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Amyloid / metabolism*
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Contrast Media / administration & dosage*
  • Contrast Media / pharmacokinetics
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Humans
  • Macaca fascicularis
  • Magnetic Resonance Imaging / methods*
  • Male
  • Mice
  • Mice, Transgenic
  • Peptide Fragments / metabolism
  • Plaque, Amyloid / diagnostic imaging*
  • Plaque, Amyloid / genetics
  • Plaque, Amyloid / metabolism
  • Presenilin-1 / genetics
  • Rats
  • Tissue Distribution


  • Amyloid
  • Amyloid beta-Protein Precursor
  • Contrast Media
  • Peptide Fragments
  • Presenilin-1