Radiolabled polymeric nanoparticles for imaging alzheimer's plaques in a mouse model of alzheimer's disease (AD)

We have shown that, clioquinol (CQ) (5-chloro-7-iodo-8 hydroxy quinoline) can be radioiodinated and has rapid brain uptake and fast clearance from the blood and brain in normal mice. In order to enhance its brain uptake and retard the fast brain clearance, we incorporated it into butylpolycyanoacrylate (BCA) nanoparticles (NP). Selective localization of ¹²⁵I CQ BCA nanoparticles was observed in autoradiograph of Alzheimer's Disease (AD) patient's postmortem brain sections. We studied its biodistribution in normal mice and experimental AD mice. AD lesions were created by administration of preformed aggregates of A-beta peptide (A□42) into hippocampus of mice using a stereotactic device. Biodistribution and ex-vivo autoradiography of the brains of mice injected with ¹²⁵I CQ BCA nanoparticles showed that: 1. nanoparticles enhanced (1.5-2 times) the brain delivery of the ¹²⁵I-CQ 2. Autoradiograph of AD brain sections showed localized uptake of the radiotracer and 3. experimental animal brains had positive autoradiogram compared to the control animals and animals injected with the free drug. Our data indicate that butyl polycyanoacrylate nanoparticles may be useful drug delivery vehicles for imaging AD with amyloid specific dyes.