| First Author | Badachhape AA | Year | 2020 |
| Journal | Sci Rep | Volume | 10 |
| Issue | 1 | Pages | 16185 |
| PubMed ID | 32999398 | Mgi Jnum | J:296341 |
| Mgi Id | MGI:6467021 | Doi | 10.1038/s41598-020-73233-7 |
| Citation | Badachhape AA, et al. (2020) 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 10(1):16185 |
| abstractText | In these preclinical studies, we describe ADx-001, an Abeta-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 beta 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. |
