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The effect of chelator type on in vitro receptor binding and stability in 177Lu-labeled cetuximab and panitumumab
Z. Novy, A. Laznickova, J. Mandikova, P. Barta, M. Laznicek, F. Trejtnar,
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články, práce podpořená grantem
Odkazy
PubMed
24889367
DOI
10.1002/jlcr.3204
Knihovny.cz E-zdroje
- MeSH
- antitumorózní látky chemie farmakologie MeSH
- buňky Hep G2 MeSH
- chelátory chemie farmakologie MeSH
- erbB receptory metabolismus MeSH
- humanizované monoklonální protilátky chemie farmakologie MeSH
- lidé MeSH
- lutecium chemie MeSH
- monoklonální protilátky chemie farmakologie MeSH
- radiofarmaka chemie farmakologie MeSH
- radionuklidy chemie MeSH
- vazba proteinů účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Monoclonal antibodies are used in the therapy of various diseases. Thanks to their high specific uptake in target tissues, these antibodies can be utilized in targeted radioimmunotherapy as carriers of radioisotopes to tumors. However, important characteristics of antibodies such as target binding and stability in the organism may be affected by various structural parameters. This study has focused on the potential influence of selected chelators on radiochemical quality and in vitro receptor binding capacity in two modified monoclonal antibodies-cetuximab and panitumumab, both ligands of the epidermal growth factor receptor (EGFR). These two antibodies were each coupled with three macrocyclic chelators (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, 1,4,7-triazacyclononane-1,4,7-triacetic acid, and 3,6,9,15-tetraazabicyclo[9.3.1]-pentadeca-1(15),11,13-triene-4-(S)-(4-isothiocyanatobenzyl)-3,6,9-triacetic acid) and labeled with lutetium-177. The stability of the preparations was checked, and the cell binding to EGFR-expressing cell lines was examined. The used method led to very stable radiolabeled preparations. The results showed that binding to the target cells was not affected by the type of chelator. All three chelators may be useful for the labeling of cetuximab and panitumumab with lutetium-177 in future preclinical or clinical studies. Our study revealed previously unpublished fact that the type of chelator selected does not affect binding of EGFR-targeted antibodies labeled with lutetium-177.
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- $a Novy, Zbynek $u Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Czech Republic; Laboratory of Experimental Medicine, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic.
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