Affiliations: [a] Texas Children’s Hospital, Houston, TX, USA | [b] University of Houston, Houston, TX, USA | [c] University of Kentucky, Lexington, KY, USA | [d] Baylor College of Medicine, Houston, TX, USA
Correspondence:
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Correspondence to: Ananth Annapragada, The Singleton Department of Pediatric Radiology, Texas Children’s Hospital, 1102 Bates Street, Suite 850, Feigin Center, Houston, TX 77030, USA. Tel.: +1 832 824 0865; E-mail: avannapr@texaschildrens.org.
Abstract: Amyloid binding molecules with greater hydrophilicity than existing ligands were synthesized. The lead candidate ET6-21 bound amyloid fibrils, and amyloid deposits in dog brain and human brain tissue ex vivo. The ligand was used to prepare novel amyloid-targeted liposomal nanoparticles. The preparation was tested in the Tg2576 and TetO/APP mouse models of amyloid deposition. Gd chelates and Indocyanine green were included in the particles for visualization by MRI and near-infrared microscopy. Upon intravenous injection, the particles successfully traversed the blood-brain barrier in these mice, and bound to the plaques. Magnetic resonance imaging (T1-MRI) conducted 4 days after injection demonstrated elevated signal in the brains of mice with amyloid plaques present. No signal was observed in amyloid-negative mice, or in amyloid-positive mice injected with an untargeted version of the same agent. The MRI results were confirmed by immunohistochemical and fluorescent microscopic examination of mouse brain sections, showing colocalization of the fluorescent tags and amyloid deposits.
