Biodistribution and pharmacokinetics of(111)In-DTPA-labelled pegylated liposomes in a human tumour xenograft model: implications for novel targeting strategies

The biodistribution and pharmacokinetics of(111)In-DTPA-labelled pegylated liposomes in tumour-bearing nude mice was studied to examine possible applications of pegylated liposome-targeted anti-cancer therapies. Nude mice received an intravenous injection of 100 μl of(111)In-DTPA-labelled pegylated liposomes, containing 0.37–0.74 MBq of activity. The t (1/2α) and t (1/2β) of(111)In-DTPA-labelled pegylated liposomes were 1.1 and 10.3 h, respectively. Tumour uptake was maximal at 24 h at 5.5 ± 3.0% ID g(–1). Significant reticuloendothelial system uptake was demonstrated with 19.3 ± 2.8 and 18.8 ± 4.2% ID g(–1)at 24 h in the liver and spleen, respectively. Other sites of appreciable deposition were the kidney, skin, female reproductive tract and to a lesser extent the gastrointestinal tract. There was no indication of cumulative deposition of pegylated liposomes in the lung, central nervous system, musculoskeletal system, heart or adrenal glands. In contrast, the t (1/2α) and t (1/2β) of unencapsulated(111)In-DTPA were 5 min and 1.1 h, respectively, with no evidence of accumulation in tumour or normal tissues. Incubation of(111)In-DTPA-labelled pegylated liposomes in human serum for up to 10 days confirmed that they are very stable, with only minor leakage of their contents. The potential applications of pegylated liposomes in the arena of targeted therapy of solid cancers are discussed. © 2000 Cancer Research Campaign