1 research outputs found
<sup>68</sup>Ga-Labeled Gold Glyconanoparticles for Exploring BloodāBrain Barrier Permeability: Preparation, Biodistribution Studies, and Improved Brain Uptake via Neuropeptide Conjugation
New tools and techniques to improve
brain visualization and assess
drug permeability across the bloodābrain 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 <sup>68</sup>Ga 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 <sup>68</sup>Ga, 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 Ā°C followed
by purification via centrifugal filtration. As a proof of principle,
a biodistribution study in rats is performed for the different <sup>68</sup>Ga-GNPs. The accumulation of radioactivity in different organs
after intravenous administration is measured by whole body PET imaging
and gamma counter measurements of selected organs. The biodistribution
of the <sup>68</sup>Ga-GNPs varies depending on the ligands, as GNPs
with the same gold core size show different distribution profiles.
One of the targeted <sup>68</sup>Ga-GNPs improves BBB crossing near
3-fold (0.020 Ā± 0.0050% ID/g) compared to nontargeted GNPs (0.0073
Ā± 0.0024% ID/g) as measured by dissection and tissue counting