Optimization of an Iodine-based Nanoparticle Contrast Agent for Molecular CT Imaging

摘要

Recent advances in CT hardware have renewed interest in the development of contrast agents for molecular CT imaging. Nanoparticle platforms are attractive for CT imaging agent development due to their ability to carry a high payload of imaging moieties, thereby facilitating signal amplification at target site, and ease of surface modification to enable selective in vivo targeting against cells/molecules of interest. In this work, we performed investigations for optimizing an iodine-based liposomal nanoparticle platform for molecular CT imaging applications. Since signal intensity is directly proportional to the imaging moiety concentration, optimization studies were performed to rationally design an iodinated nanoparticle construct with maximal iodine carrying capacity. The effect of particle size, liposomal bilayer composition, iodine moiety and starting iodine concentration were systematically investigated. The in vitro stability of the optimal formulation was evaluated using plasma assay and the in vivo stability was tested by performing longitudinal micro-CT imaging in live animals. Simulations were performed to study the effects of iodine per nanoparticle and iodine contrast sensitivity on detectability of nanoparticles per image voxel. In vitro optimization studies demonstrated that particle size, type of iodine moiety and starting iodine concentration strongly influenced the iodine loading per nanoparticle. A nanoparticle composition was identified that demonstrated highest iodine loading capacity (~ 8 million iodine atoms per particle). Micro-CT imaging demonstrated in vivo stability of the high-iodine containing nanoparticle construct. Simulation studies demonstrated a non-linear effect of iodine contrast sensitivity and image voxel size on the limit of nanoparticle detectability.