Novel nanoparticle contrast agents for blood pool imaging

Blood pool imaging plays an essential role in diagnostic medicine because of the high prevalence of intravascular abnormalities in many pathological processes. Contrast agents are commonly used in several imaging applications as a means to increase the signal from the vascular compartment. Unfortunately, the role of contrast agents has been limited in the evaluation of smaller vessels, due to the long scan times required to obtain high resolution images.;To overcome the limitations with conventional contrast agents, the development of nanoparticle contrast agent, based on liposomal platform technology, is described in this work. Liposomal contrast agents encapsulating iodine molecules for use in Computed Tomography (CT) imaging and gadolinium molecules for use in Magnetic Resonance (MR) imaging were synthesized. Characterization studies of both the class of liposomal agents demonstrated good in vitro and in vivo stability.;To investigate their potential in vivo, the liposomal MR agent was used for high-resolution, vascular imaging of the rat spine region. The intravascular nature of liposomal MR agent enabled visualization of several important micro-vascular features with high contrast-to-noise ratio. The application of liposomal MR agent to image the spinal cord injury indicated that the extravasation of liposomes into the injured region is presumably the rate limiting step for the detection of injury.;The liposomal CT agent was used for high-resolution, micro-CT imaging in a mouse model. The agent demonstrated long residence time in the blood pool and very high attenuation within the microvessels. The intravascular nature and the long circulation property of liposomal CT also enabled cardiac imaging with respiratory and cardiac gating. Tumor imaging studies demonstrated excellent visualization of the microvessels. Investigating their utility in characterizing tumors based on nanoparticle extravasation showed that the transport of liposomes through the tumor tissue and the low sensitivity of micro-CT to contrast agents represent major barriers. The pharmacokinetic model developed to study the transport of liposomal CT in tumors also predicted the experimental results reasonably well. The liposomal contrast agent is the first demonstration of a blood pool agent for high resolution in vivo imaging.