A novel derivative of the chelon desferrioxamine for site-specific conjugation to antibodies.

Détails

ID Serval
serval:BIB_20BD28C33279
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
A novel derivative of the chelon desferrioxamine for site-specific conjugation to antibodies.
Périodique
International Journal of Cancer
Auteur(s)
Pochon S., Buchegger F., Pélegrin A., Mach J.P., Offord R.E., Ryser J.E., Rose K.
ISSN
0020-7136 (Print)
ISSN-L
0020-7136
Statut éditorial
Publié
Date de publication
1989
Peer-reviewed
Oui
Volume
43
Numéro
6
Pages
1188-1194
Langue
anglais
Résumé
We describe the preparation of the modified chelator aminooxyacetyl-ferrioxamine, and the replacement of its iron atom by 67Ga at high specific activity. The aminooxy function of this compound was allowed to react with the aldehyde groups generated by the periodate oxidation of the oligosaccharide of a mouse IgG1 monoclonal antibody (MAb) directed against carcino-embryonic antigen (CEA). The use of the aminooxy group allowed a stable bond to be formed between the chelon and the antibody with no need for reduction. Iron was removed from the ferrioxamine moiety and replaced by 67Ga either before or after conjugation of the chelon to the antibody. In either case the labelled antibody was injected into nude mice bearing a human colon carcinoma having the appropriate antigenicity. Unoxidized antibody, labelled with 125I by conventional methods, was co-injected as an internal control. Additional control experiments were carried out with a non-immune IgG using the same 67Ga-labelled modified chelon as above. The in vivo distribution of the modified antibodies was evaluated at various times between 24 and 96 hr after injection. The methods used were gamma-camera imaging and, more quantitatively, gamma-counting of the various organs after dissection. Interestingly, with the metal-chelon-labelled antibody, the intensity and specificity of tumor labelling was comparable and in some cases superior to the results obtained with radio-iodinated antibody. In particular, there was almost no increase in liver and spleen uptake of radioactive metal relative to radio-iodine, contrary to what has been observed with most antibodies labelled with 111In after conjugation with DTPA.
Mots-clé
Animals, Antibodies, Monoclonal/diagnostic use, Deferoxamine/analogs & derivatives, Deferoxamine/diagnostic use, Gallium Radioisotopes/diagnostic use, Immunoglobulin G/metabolism, Immunotoxins/diagnostic use, Immunotoxins/metabolism, Iodine Radioisotopes/diagnostic use, Mice, Mice, Nude, Structure-Activity Relationship, Tissue Distribution
Pubmed
Web of science
Création de la notice
25/01/2008 12:27
Dernière modification de la notice
20/08/2019 13:57
Données d'usage