Synthesis and Evaluation of Oleanolic Acid-Conjugated Lactoferrin for β-Amyloid Plaque Imaging

${\beta}$-Amyloid accumulation in the brain is a pathological hallmark of Alzheimer's disease (AD). Since early detection of ${\beta}$-amyloid may facilitate more successful and timely therapeutic interventions, many investigators have focused on developing AD diagnostic reagents that can penetrate the blood-brain barrier (BBB). Oleanolic acid (OA) is a substance found in a variety of plants that has been reported to prevent the progression of AD in mice. In this study, we synthesized and evaluated a new radioligand in which OA was conjugated to lactoferrin (Lf, an iron-binding glycoprotein that crosses the BBB) for the diagnosis of AD. In an in vitro study in which OA-Lf was incubated with ${\beta}$-amyloid (1-42) aggregates for 24 h, we found that OA-Lf effectively inhibited ${\beta}$-amyloid aggregation and fibril formation. In vivo studies demonstrated that $^{123}I$-OA-Lf brain uptake was higher than$^{123}I$-Lf uptake. Therefore, radiolabeled OA-Lf may have diagnostic potential for ${\beta}$-amyloid imaging.