Biodistribution and tumour localisation of a daunomycin-monoclonal antibody conjugate in nude mice with human tumour xenografts.
The blood kinetics and tissue distribution of a conjugate of daunomycin and a monoclonal antibody (791T/36) have been examined in mice, including nude mice with human tumour xenografts reactive with the antibody. For this the antibody moiety of the conjugate was labelled with 125I and the drug moiety assayed by radioimmunoassay. After radioiodination, the preparation had an immunoreactive fraction in isotopic binding tests with 791T cells of 74%. Both drug and antibody moieties were precipitable with anti-mouse Ig anti-serum. Following i.v. injection, blood clearance of the two components of the conjugate was essentially identical, and with the serum-borne conjugate both radiolabel and drug were co-precipitable. In mice with 791T xenografts, the tumour showed localisation of both drug and antibody moieties and at the time of analysis (3 days) tumour levels of drug were over 100 times those seen with free drug. In parallel studies with mice with antigen negative xenografts, there was no preferential localisation of antibody or drug moieties of the conjugate. These studies have shown in vivo stability of this conjugate, and site-specific targetting of an anti-tumour anthracycline.
Pimm
M V
MV
Cancer Research Campaign Laboratories, University of Nottingham, U.K.
Paul
M A
MA
Ogumuyiwa
Y
Y
Baldwin
R W
RW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D003630:Daunorubicin / Q000493:pharmacokinetics*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000378:metabolism*; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D003630:Daunorubicin