Human recombinant TNF-alpha on localization of 90Y-radioantibody in human tumour xenografts.
The effect of recombinant human tumour necrotic factor-alpha (TNF-alpha) on the intratumour and whole-body distributions of 90Y-labelled C110 anticarcinoembryonic antigen (CEA) monoclonal antibody (MAb) was studied using nude mice bearing two different tumours. The nude mice were injected subcutaneously with the CEA-positive LS174T colorectal cancer xenograft and the CEA-negative H-MESO-1 malignant mesothelioma xenograft. One hour before injection of radiolabelled MAb, mice were injected intravenously with human recombinant TNF-alpha (3 mg per mouse) or saline, and biodistributions of radiolabel were determined by tissue counting and whole-body autoradiography (ARG). Twenty-four hours after injection, TNF-alpha administration increased radioactivity in the LS174T tumour by 57% (17.30 +/- 1.61 vs. 9.83 +/- 1.55% ID g-1, P < 0.01), while decreasing radioactivity in blood and other normal organs. Diminished but similar effects on radioantibody biodistribution were seen at 48 and 72 hours. TNF-alpha did not affect specific MAb localization in the control H-MESO xenograft. Tumour:blood ratios were increased from 0.7 to 1.7 at 24 h with TNF-alpha administration. Pretreatment with TNF-alpha may be of value in increasing specific localization of monoclonal antibodies in tumour tissue.
Matsushita
T
T
Department of Nuclear Medicine, University of Massachusetts Medical Center, Worcester 01655, USA.
Griffin
T W
TW
Yao
Z
Z
Delichatsios
H
H
Brill
A B
AB
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002272:Carcinoembryonic Antigen / Q000276:immunology; D006801:Humans; D000922:Immunotoxins / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000378:metabolism; D011994:Recombinant Proteins; D014018:Tissue Distribution / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015021:Yttrium Radioisotopes
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D000922:Immunotoxins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D015021:Yttrium Radioisotopes