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

Details

Serval ID
serval:BIB_20BD28C33279
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A novel derivative of the chelon desferrioxamine for site-specific conjugation to antibodies.
Journal
International Journal of Cancer
Author(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
Publication state
Published
Issued date
1989
Peer-reviewed
Oui
Volume
43
Number
6
Pages
1188-1194
Language
english
Abstract
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.
Keywords
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
Create date
25/01/2008 11:27
Last modification date
20/08/2019 12:57
Usage data