title: The effect of chelator type on in vitro receptor binding and stability in 177Lu-labeled cetuximab and panitumumab.
abstract: 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 Our study revealed previously unpublished fact that the type of chelator selected does not affect binding of EGFR-targeted antibodies labeled with lutetium-177.
authors.affiliation: 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.
authors.forename: Zbynek
authors.initials: Z
authors.lastname: Novy
authors.forename: Alice
authors.initials: A
authors.lastname: Laznickova
authors.forename: Jana
authors.initials: J
authors.lastname: Mandikova
authors.forename: Pavel
authors.initials: P
authors.lastname: Barta
authors.forename: Milan
authors.initials: M
authors.lastname: Laznicek
authors.forename: Frantisek
authors.initials: F
authors.lastname: Trejtnar
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D000068818:Cetuximab; D002614:Chelating Agents / Q000737:chemistry / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D008187:Lutetium / Q000737:chemistry; D000077544:Panitumumab; D011485:Protein Binding / Q000187:drug effects; D011868:Radioisotopes / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D002614:Chelating Agents; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D008187:Lutetium; D000077544:Panitumumab; D066246:ErbB Receptors; D000068818:Cetuximab
keywords: EGFR; monoclonal antibody; radioimmunotherapy; radiolabeling; tumor targeting