This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The primary goal of this proposal is to overcome the confounding effects of a leaky blood brain barrier in tumors by using a novel CT contrast agent, iodinated liposome. Liposomes are microscopic spherical vesicles constructed of phospholipid bilayers that can encapsulate the iodinated contrast agent. Vesicle size, chemical affinity, and thermal (or pH) sensitivities can be engineered. We will use polyethylene glycol (PEG)-coated liposome with an intravascular circulation half-life of 6-8 hours. These characteristics allow blood pool imaging for several hours after a simple IV injection, and should also decrease the rate of extravasation of the agent into the tumor interstitium. The relative enhancement of a voxel on a CT study is proportional to the intravoxel concentration of contrast agent. Agents that behave as true bloodpool agents on the time scale of this experiment should remain within the intravascular space. Therefore, relative enhancement of a voxel should be proportional to the cerebral blood volume (CBV). This should allow for direct measurement of CBV, rather than the need for using a deconvolution approach. Moreover, reinjection with a standard iodinated contrast agent can be performed soon afterward, and a more accurate permeability surface product determination can be obtained because CBV has been accurately measured.
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