Comparison of Succinimidyl [125I]Iodobenzoate with Iodogen Iodination Methods to Study Pharmacokinetics and ADME of Biotherapeutics

• Published in: Pharmaceutical research 2014-10, Vol.31 (10), p.2810-2821
• Main Authors: Chen, Jianqing, Wang, Mengmeng, Joyce, Alison, DeFranco, David, Kavosi, Mania, Xu, Xin, O’Hara, Denise M.
• Format: Article
• Language: English
• Subjects: Absorption, Physiological; Animals; Antibodies, Monoclonal - blood; Antibodies, Monoclonal - pharmacokinetics; Area Under Curve; Benzoates - chemistry; Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Drug Monitoring - methods; Electrophoresis, Polyacrylamide Gel; Iodine Radioisotopes; Iodobenzoates - chemistry; Isotope Labeling - methods; Labeling; Medical Law; Metabolic Clearance Rate; Methods; Mice; Pharmacology; Pharmacology/Toxicology; Pharmacy; Proteins; Research Paper; Rodents; Tissue Distribution; Trialkyltin Compounds - chemistry; Urea - analogs & derivatives; Urea - chemistry
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-014-1378-3

ABSTRACT Purpose To assess the application of succinimidyl iodobenzoate (SIB) iodination method in labeling biotherapeutics to study their pharmacokinetics (PK) and biodistribution. Method An IgG molecule (protein-01) and a 40 KDa protein (protein-02) were evaluated. Pharmacokinetics (PK) and biodistribution of the radiolabeled IgG ( 125 I-protein-01) in mice compared parameters from SIB and Iodogen protein iodination labeling methods. In addition, PK of radiolabeled 40 KDa protein ( 125 I-protein-02) using SIB was compared with non-labeled protein-02 analyzed by ligand binding assay (LBA). Results Up to 72 h following a single IP injection to mice, the percentage of “free-label” determined by the soluble counts after TCA precipitation to total radioactivity in serum samples was 2.8–49.4% vs.