Liposomes and micelles to target the blood pool for imaging purposes

The blood pool is among body compartments of a special interest for imaging using magnetic resonance (MR) and computed tomography (CT), since with the help of selective blood-pool contrast agents blood perfusion and various c ardiac parameters as well as a status of the blood flow and vascular system in any organ can be evaluated. Blood pool-specific imaging agents can also provide minimally invasive angiography, image guidance of minimally invasi ve procedures, oncologic imaging of angiogenesis, ascertaining organ blood volume, and identifying hemorrhage. Particulate contrast agents (such as li posomes and micelles) whose distribution is limited to the blood pool, shou ld have a size larger than fenestrated capillaries (> 10 nm), contain the r eporter (paramagnetic or radiopaque) moiety structurally incorporated withi n the particulate, and be able to stay in the blood long enough to obtain c linically useful images. We describe here a new generation of long-circulat ing Gd-loaded liposomes and iodine-loaded micelles to provide an efficient blood pool MR and CT imaging, respectively. In this study, we developed the optimized protocol to prepare a liposomal MR contrast agent with high rela xivity and narrow size distribution. Liposomes were loaded with Gadolinium (Gd) via so called polychelating amphiphilic polymer (PAP) that represents a low-molecular-weight DTPA-polylysine linked via its N-terminus to a lipid anchor, NGPE-PE. Gd-containing liposomes were additionally modified with P EG to provide the longevity in vivo. We demonstrated also that upon the int ravenous administration in rabbits and dogs, a new preparation causes prolo nged decrease in the blood T1 value, permits to obtain sharp and clear MR i mages of the vasculature, and may be considered as a potential contrast age nt for MRI of the blood pool. In addition, to prepare micellar contrast age nts for CT blood-pool imaging, we synthesized an iodine-containing amphiphi lic block-copolymer consisting of methoxypoly(ethyleneglycol) and poly[epsi lon ,N-(triiodobenzoyl)]-L-lysine. In aqueous solutions, it forms stable mi celles with an average diameter of 80 nm and an iodine content of 35-40% wt . Iodine-containing micelles were intravenously injected into rats and rabb its at a dose of 170 mg I/kg and produced significant and sustained enhance ment of the blood pool (aorta and heart), liver and spleen for a period of at least 3 hours providing clear and informative CT images.