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Biodistribution and tumour localization of a methotrexate‐monoclonal‐antibody 791T/36 conjugate in nude mice with human tumour xenografts
Author(s) -
Pimm M. V.,
Clegg Jane A.,
Garnett M. C.,
Baldwin R. W.
Publication year - 1988
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910410620
Subject(s) - conjugate , biodistribution , antibody , monoclonal antibody , methotrexate , moiety , in vivo , chemistry , pharmacokinetics , radioimmunoassay , pharmacology , microbiology and biotechnology , biology , immunology , biochemistry , in vitro , stereochemistry , mathematical analysis , mathematics
The blood kinetics and tumour localization of a conjugate of methotrexate (MTX) and MAb 79IT/36 were examined in nude mice with human tumour xenografts. The antibody moiety of the conjugate was detected by labelling with 125 I and the drug moiety was assayed using a radioimmunoassay for methotrexate. After radio rodination, the drug moiety was co‐precipitable with the radiolabel when TCA or rabbit anti‐mouse IgG antiserum was used. Following i.v. injection, serum kinetics of both the antibody and the drug moieties of the conjugate were essentially similar, and the integrity of serum‐borne conjugate was confirmed by the co‐precipitation of radiolabel and drug. The radiolabelled antibody moiety of the conjugate localized in tumour xenografts, with 5‐7% of the injected dose being present per gram of tissue within 6 hr of injection, and the levels were maintained for up to 4 days. Analysis of tumour levels of the MTX moiety showed a progressive uptake over the 4‐day observation period with up to 4% of the injected dose being present per gram of tumour when the experiment was terminated. Parallel studies with free MTX showed rapid clearance from the blood and a maximum of 0.354b of the dose/g of tumour 30 min after injection. Control immunogiobulin conjugated to MTX did not show tumour localization of either the antibody or the drug moieties. These studies confirm that in vivo MTX remains bound to antibody in this type of drug antibody conjugate and demonstrate site‐specific targeting of this therapeutic agent.