Development of targeted medical imaging contrast agents: Assessment of cellular interactions using integrated optical nanoparticle labels

Objectives Perfluorocarbons (PFCs) are promising targeted medical imaging contrast agents for ultrasound, magnetic resonance, and X-ray/CT imaging. PFCs labeled with optical imaging agents can allow complementary assessment of contrast agent interactions directly with cells in both in vitro and in vivo systems.

Methods Fluorescent quantum dot (QD) nanoparticles were dispersed in PFCs after surface fluorination, and were emulsified to form sub-micron, QD-tagged PFC droplets. The in vitro multi-modal imaging properties of the nanoparticle-labeled PFC agents were assessed in macrophage cells as a function of incubation time and agent surface charge. In vivo PFC agent tolerability and biodistribution were assessed in a rabbit model.

Results The QD-tagging of the PFC agent allowed time- and charge-dependent uptake of different PFC droplets into cells to be optically assessed in vitro. The uptake of non-ionic PFC agents by macrophage cells after incubation for 2 hours was found to be almost two folds lower than the uptake of anionic PFC agents. In the rabbit model, QD-tagged PFC agents were optically observed in histology sections of the liver, spleen and lung 24 hours after injection.

Conclusions This novel QD-tagged PFC agent was used to directly assess the surface-dependent uptake profile of PFC agents by cells in vitro. The QD fluorescence was optically detectable in histology sections after in vivo injection in rabbits. This QD-PFC agent may be used for the effective pre-clinical, quantitative evaluation of new PFC-based medical imaging contrast agents.