Gold nanoparticles-based SPECT/CT imaging probe targeting for vulnerable atherosclerosis plaques

Abstract

In order to realize accurate localization and precise evaluation of vulnerability of atherosclerotic plaques via dual-modal imaging, gold nanoparticles (GNPs) were firstly caped with a thin amino-PEGs cover and then conjugated with the targeting molecular Annexin V and radionuclide Tc-99m simultaneously to form SPECT/CT imaging probe targeting apoptotic macrophages. The as-synthesized (99m)Tc-GNPs-Annexin V was with uniform size (30.2 ± 2.9 nm) and high labeling rate (98.9 ± 0.5%) and stability. Targeting ability of Annexin V for apoptotic macrophages was kept and enhanced. For macrophages with 30% apoptosis, cellular uptakes of 3.52 ± 0.35% for (99m)Tc-GNPs-Annexin V, 2.41 ± 0.53% for (99m)Tc-GNPs and 1.68 ± 0.36% for (99m)Tc-Annexin V were achieved after 2 h incubation. ApoE knock out mice with high fat diet-induced atherosclerosis were scanned via (99m)Tc-GNPs-Annexin V SPECT/CT. With the introduction of targeting molecules, imaging probe was more efficient in accumulating in apoptotic macrophages. In practical evaluation, CT helps to restrict the lesions depiction more accurately, meanwhile, SPECT imaging intensity correlated with pathological changes tightly. In conclusion, Annexin V-modified hybrid gold nanoparticles were successfully synthesized, and this imaging system helped to better localize and diagnose those vulnerable AS plaques via specific targeting the apoptotic macrophages.

Keywords: Annexin V; Apoptotic macrophages; Gold nanoparticles; SPECT/CT; Vulnerable atherosclerosis plaques.