Tumour targeting with antibody-coupled liposomes: failure to achieve accumulation in xenografts and spontaneous liver metastases.
The potential of small unilamellar liposomes coupled to anti-tumour monoclonal antibodies (immunoliposomes) to accumulate in solid tumour tissue was tested in two systems, i.e. a human malignant melanoma xenografted into nude mice and a syngeneic murine lymphoma ESb.Mp exhibiting spontaneous metastasis to the liver. Both monoclonal antibodies tested were partly released from immunoliposomes within a few hours, thus generating a seemingly constant level of circulating antibody. Nevertheless it was possible to follow the biodistribution of intact immunoliposomes by virtue of a radioiodine label incorporated into the lipid moiety. It was found that in both tumor systems, though they differed with respect to the size of lesions and maybe also to the vascular architecture of surrounding tissue, immunoliposome uptake was virtually nil. The blockade of uptake into solid tumour tissue was caused by the limited availability of immunoliposomes due to their moderate stability, but especially by the inability of the particulate carrier to extravasate.
Matzku
S
S
Institute of Radiology and Pathophysiology, German Cancer Research Center, Heidelberg, Federal Republic of Germany.
Krempel
H
H
Weckenmann
H P
HP
Schirrmacher
V
V
Sinn
H
H
Stricker
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D004337:Drug Carriers; D006801:Humans; D007167:Immunotherapy; D000922:Immunotoxins / Q000493:pharmacokinetics; D008081:Liposomes / Q000493:pharmacokinetics*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000556:secondary* / Q000628:therapy; D008223:Lymphoma / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D008545:Melanoma / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D051379:Mice; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D004337:Drug Carriers; D000922:Immunotoxins; D008081:Liposomes