ABSTRACT
To better understand the mechanism of uptake of sterically stabilized (Stealth®) liposomes by various tissues, and to the improve therapeutic efficacy of encapsulated agents, it would be advantageous to know the pathway and the final localization of liposomes in tissues following IV injection. Radioactive agents, such as 67Ga or 11 1Jn, were very commonly employed as liposome markers in pharmacokinetics and biodistribution studies. 1•2 The resultant levels of radioactivity measured in relevant tissues proved that Stealth liposomes have prolonged circulation time in blood and reduced uptake by the reticuloendothelial system (RES),3A and increased accumulation in solid tumors.5-7 Instead of radioactivity measurements, people also use images of radiolabeled liposomes to monitor tissue distribution by gamma scanning.8 Despite extensive studies on tissue distribution, it is still not known where liposomes are localized at the cellular level in most tissues following IV injection. Are there any tissues or pathologic conditions where the liposomes can cross blood vessel endothelium and basal lamina? If liposomes can extravasate and accumulate in pathologic regions, such as tumors, are they internalized by tumor cells?
