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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.
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