PEG-coated lipid vesicles with encapsulated technetium-99m as blood pool agents for nuclear medicine

Unilamellar lipid vesicles of average diameter 200 nm containing 30 mM glutathione were internally labeled with 99mTc using exametazime (HMPAO) to transport technetium across the lipid bilayer. Vesicles were prepared both in the absence and presence of the lipid-polymer conjugate phosphatidylethanolamine-monomethoxy polyethylene glycol 5000 (PE-MPEG). Labeling efficiency both in the absence and presence of surface polymer was greater than 95% and the vesicles retained greater than 95% of their contents when incubated against 50% human serum at 37 degrees C for 12 h. When introduced intravenously into rabbits at a total lipid concentration of 4 mumol/kg (3.5 mg/kg), radiolabeled vesicles without surface polymer were rapidly cleared from the circulation with a half-life of approx. 30 min and delivered to liver and spleen, however if the lipid vesicles were prepared containing 3 or 4.5 mol percent PE-MPEG the circulation half-life of the label was approx. 5 and 10 h, respectively, and RES uptake was suppressed. These studies confirm a previous report of the utility of exametazime for preparing 99mTc-labeled lipid vesicles and demonstrate that extended circulation half-lives are achievable for 99mTc-labeled vesicles without recourse to high lipid doses and reticuloendothelial blockade. Applications to use exametazime as a blood pool marker in nuclear medicine are discussed.