Biodistribution and tumour localization of a methotrexate-monoclonal-antibody 791T/36 conjugate in nude mice with human tumour xenografts

✍ Scribed by M. V. Pimm; Jane A. Clegg; M. C. Garnett; R. W. Baldwin

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: French
• Weight: 717 KB
• Volume: 41
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910410620

✦ Synopsis

The blood kinetics and tumour localization of a conjugate of methotrexate (MTX) and MAb 791T136 were examined i n nude mice with human tumour xenografts. The antibod moiety of the conjugate was detected by labelling with l2J and the drug moiety was assayed using a radioimmunoassay for methotrexate. After radioiodination, the drug moiety was co-precipitable with the radiolabel when TCA or rabbit antimouse 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 serumborne 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 M T X moiety showed a progressive uptake over the 4-day observation period with up t o 4% of the injected dose being present per gram of tumour when the experiment was terminated. Parallel studies with free M T X showed rapid clearance from the blood and a maximum of 0.35% of the dose/g of tumour 30 min after injection.

Control immunoglobulin conjugated t o M T X did not show tumour localization of either the antibody or the drug moieties. These studies confirm that in vivo M T X remains bound t o antibody in this type of drug antibody conjugate and demonstrate site-specific targeting of this therapeutic agent.