title: Site-Specific Radioiodination of HER2-Targeting Affibody Molecules using 4-Iodophenethylmaleimide Decreases Renal Uptake of Radioactivity.
abstract: Affibody molecules are small scaffold-based affinity proteins with promising properties as probes for radionuclide-based molecular imaging. However, a high reabsorption of radiolabeled Affibody molecules in kidneys is an issue. We have shown that the use of (125)I-3-iodo-((4-hydroxyphenyl)ethyl)maleimide (IHPEM) for site-specific labeling of cysteine-containing Affibody molecules provides high tumor uptake but low radioactivity retention in kidneys. We hypothesized that the use of 4-iodophenethylmaleimide (IPEM) would further reduce renal retention of radioactivity because of higher lipophilicity of radiometabolites. An anti-human epidermal growth factor receptor type 2 (HER2) Affibody molecule (ZHER2:2395) was labeled using (125)I-IPEM with an overall yield of 45±3 %. (125)I-IPEM-ZHER2:2395 bound specifically to HER2-expressing human ovarian carcinoma cells (SKOV-3 cell line). In NMRI mice, the renal uptake of (125)I-IPEM-ZHER2:2395 (24±2 and 5.7±0.3 % IA g(-1)at 1 and 4 h after injection, respectively) was significantly lower than uptake of (125)I-IHPEM-ZHER2:2395 (50±8 and 12±2 % IA g(-1)at 1 and 4 h after injection, respectively). In conclusion, the use of a more lipophilic linker for the radioiodination of Affibody molecules reduces renal radioactivity.
authors.affiliation: Biomedical Radiation Sciences, Faculty of Medicine, Uppsala University 751 85, Uppsala, Sweden.
authors.forename: Joanna
authors.initials: J
authors.lastname: Strand
authors.affiliation: Preclinical PET Platform, Department of Medicinal Chemistry, Faculty of Pharmacy, Uppsala University 751 23, Uppsala, Sweden.
authors.forename: Patrik
authors.initials: P
authors.lastname: Nordeman
authors.affiliation: Biomedical Radiation Sciences, Faculty of Medicine, Uppsala University 751 85, Uppsala, Sweden.
authors.forename: Hadis
authors.initials: H
authors.lastname: Honarvar
authors.affiliation: Biomedical Radiation Sciences, Faculty of Medicine, Uppsala University 751 85, Uppsala, Sweden.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Altai
authors.affiliation: Preclinical PET Platform, Department of Medicinal Chemistry, Faculty of Pharmacy, Uppsala University 751 23, Uppsala, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Orlova
authors.affiliation: Preclinical PET Platform, Department of Medicinal Chemistry, Faculty of Pharmacy, Uppsala University 751 23, Uppsala, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Larhed
authors.affiliation: Biomedical Radiation Sciences, Faculty of Medicine, Uppsala University 751 85, Uppsala, Sweden.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Tolmachev
keywords: affibody molecules; drug design; iodophenethylmaleimide; radiolabeling; radiopharmaceuticals