68Ga-Labeled Gold Glyconanoparticles for Exploring Blood–Brain Barrier Permeability: Preparation, Biodistribution Studies, and Improved Brain Uptake via Neuropeptide Conjugation

TLDR: The synthesis of novel water-soluble and biocompatible glucose-coated gold nanoparticles (GNPs) carrying BBB-permeable neuropeptides and a chelator of the positron emitter (68)Ga as a PET reporter for in vivo tracking biodistribution is developed.

Abstract: New tools and techniques to improve brain visualization and assess drug permeability across the blood–brain barrier (BBB) are critically needed. Positron emission tomography (PET) is a highly sensitive, noninvasive technique that allows the evaluation of the BBB permeability under normal and disease-state conditions. In this work, we have developed the synthesis of novel water-soluble and biocompatible glucose-coated gold nanoparticles (GNPs) carrying BBB-permeable neuropeptides and a chelator of the positron emitter 68Ga as a PET reporter for in vivo tracking biodistribution. The small GNPs (2 nm) are stabilized and solubilized by a glucose conjugate. A NOTA ligand is the chelating agent for the 68Ga, and two related opioid peptides are used as targeting ligands for improving BBB crossing. The radioactive labeling of the GNPs is completed in 30 min at 70 °C followed by purification via centrifugal filtration. As a proof of principle, a biodistribution study in rats is performed for the different 68Ga-GNP...