title: 17AAG-induced internalisation of HER2-specific Affibody molecules.
abstract: The geldanamycin derivative 17-allylamino-17-demethoxygeldanamycin (17-AAG) is known to induce internalisation and degradation of the otherwise internalisation-resistant human epidermal growth factor receptor 2 (HER2) receptor. In the present study, 17-AAG was used to increase internalisation of the HER2-specific Affibody molecule ABY-025. The cellular redistribution of halogen-labelled211At-ABY-025 and radiometal-labelled111In-ABY-025 following treatment with 17-AAG was studied. 17-AAG treatment of SKOV-3 human ovarian carcinoma and SKBR-3 human breast carcinoma cells to some extent shifted the localisation of111In-ABY-025 from the cell surface to intracellular compartments in the two cell lines. ABY-025 labelled with the high-linear energy transfer α emitter211At was also internalised to a higher degree; however, due to its physiological properties, this nuclide was excreted faster. The results indicate that 17-AAG may be used to facilitate cell-specific intracellular localisation of a suitable cytotoxic or radioactive agent coupled to ABY-025 in HER2-overexpressing cells.
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, SE-75185 Uppsala, Sweden.
authors.forename: Lovisa
authors.initials: L
authors.lastname: Göstring
authors.affiliation: Department of Radiation Physics, Sahlgrenska Academy, University of Gothenburg, SE-41345 Gothenburg, Sweden.
authors.forename: Sture
authors.initials: S
authors.lastname: Lindegren
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, SE-75185 Uppsala, Sweden; Swedish Radiation Safety Authority, SE-17116, Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Gedda
keywords: 17-AAG; Affibody molecule; HER2; radiohalogen; radiometal