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

All methods were carried out in accordance with relevant guidelines and regulations.

ADx-001

ADx-001 was provided as a sterile, ready-to-use injectable liquid (Alzeca Biosciences, Houston, USA). ADx-001 is comprised of PEGylated liposomes in a 150 mM NaCl/10 mM Histidine buffer. The liposomes incorporate Gd(III)-DSPE-DOTA (the macrocyclic gadolinium imaging moiety, Gd(III)-DOTA, conjugated to a phospholipid, 1,2-Distearoyl-sn-glycero-3-phosphorylethanolamine, DSPE) and ET3-73 (amyloid plaque targeting moiety, displaying a styryl-pyrimidine terminal on DSPE-PEG-3500,1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide(polyethylene glycol)-3500]) in the bilayer (Fig. 1). The overall Gd concentration is 25 mM. Liposome particle size measured by dynamic light scattering is 140 nm. Zeta potential was ~ − 38 mV, consistent with PEGylated liposomes³⁵.

Animal studies

Mouse…