Liposomal blood pool agents for nuclear medicine and magnetic resonance imaging

Abstract

Polymer-coated lipid vesicles labeled with either a radionuclide such as technetium-99m or a paramagnetic cation such as gadolinium or manganese, exhibit an extended half-life in the circulation and reduced reticuloendothelial uptake, and are of potential utility as vascular imaging agents for both nuclear medicine and magnetic resonance. For nuclear medicine applications, lipid vesicles may be prepared with radionuclide either attached to the membrane surface by means of a suitable chelate or else encapsulated within the vesicle and offer two principle advantages compared to radiolabeled red blood cells, (i) vesicle can be prepared prior to patient arrival thereby minimizing delays and scheduling difficulties and (ii) known drug interferences are eliminated. The surface-labeling approach is technically more simple and is better suited to the production of vesicles in a pharmaceutically-acceptable form ready for labeling, however encapsulation results in vesicles which exhibit less renal clearance of entrapped label. The limitations of each approach in real clinical practice are not yet evident. For magnetic resonance applications, paramagnetically-labeled vesicles would be a superior vascular marker compared to small molecular weight paramagnetic chelates and may prove useful for blood volume and perfusion measurements. Surface-associated chelates are the approach of choice for a variety of reasons including increased relaxivity and reduced lipid dose compared to vesicles with entrapped paramagnetic chelates. The presence of polymer on the membrane surface has no effect upon die relaxivity of paramagnetic chelates eitiier entrapped widiin the vesicle or bound to the membrane surface.