Influence of tumour size on uptake of(111)ln-DTPA-labelled pegylated liposomes in a human tumour xenograft model.
The relationship between tumour size and uptake of(111)In-DTPA-labelled pegylated liposomes has been examined in a human head and neck cancer xenograft model in nude mice. The mean tumour uptake of(111)In-labelled pegylated liposomes at 24 hours was 7.2 +/- 6.6% ID/g. Liposome uptake for tumours < 0.1 g, 0.1-1.0 g and > 1.0 g was 15.1 +/- 10.8, 5.9 +/- 2.2 and 3.0 +/- 1.3% ID/g, respectively. An inverse correlation between tumour weight and liposome uptake was observed by both Spearman's rank correlation test (r(s)= - 0.573, P< 0.001) and Pearson's correlation coefficient (r(s)= - 0.555, P< 0.001). For 18 tumours with macroscopic central necrosis, the ratio of uptake in the tumour rim relative to the necrotic tumour core was 11.2 +/- 6.4. Measurement of tumour vascular volume for tumours of various sizes revealed an inverse correlation between tumour weight and tumour vascular volume (Spearman's rank correlation test, r(s)= - 0.598, P< 0.001), consistent with poor or heterogeneous vascularization of larger tumours. These data have important implications for the clinical application of pegylated liposome targeted strategies for solid cancers which are discussed in detail.
Harrington
K J
KJ
ICRF Oncology Unit, Imperial College of Science, Technology and Medicine, Hammersmith Hospital, 150 DuCane Road, London, W12 0HS, UK.
Rowlinson-Busza
G
G
Syrigos
K N
KN
Abra
R M
RM
Uster
P S
PS
Peters
A M
AM
Stewart
J S
JS
D000818:Animals; D002614:Chelating Agents / Q000493:pharmacokinetics*; D005260:Female; D006258:Head and Neck Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007205:Indium Radioisotopes / Q000493:pharmacokinetics*; D008081:Liposomes / Q000378:metabolism / Q000493:pharmacokinetics; D051379:Mice; D008819:Mice, Nude; D009336:Necrosis; D009368:Neoplasm Transplantation; D004369:Pentetic Acid / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000378:metabolism; D014407:Tumor Cells, Cultured
D002614:Chelating Agents; D007205:Indium Radioisotopes; D008081:Liposomes; D011092:Polyethylene Glycols; D004369:Pentetic Acid