Study of renal transport mechanisms of radiolabeled antibodies

Charles University in Prague, Faculty of Pharmacy in Hradec Kralove Department: Department of Pharmacology and Toxicology Candidate: Mgr. Jana Kanokova Supervisor: Doc. PharmDr. Frantisek Trejtnar, CSc. Title of rigorous thesis: Study of renal transport mechanisms of radiolabeled antibodies Utilization of monoclonal antibodies belongs to one of the important strategies in the treatment of oncological diseases. This treatment has a great advantage in precise focusing on the target structure with minimal damage to surrounding non-target tissue. The antibodies against the receptor for epidermal growth factor (EGFR) expressed in higher rate by variety of tumor types represent one of the important group. Nowadays oncology utilizes both unconjugated antibodies, and the ones conjugated with other effector components, e.g. cytostatic agents, radionuclides, toxins. One of the important limits for the antibodies conjugated with radionuclides appears to be their potential accumulation in kidneys with subsequent radiotoxic damage to the kidney tissue. The aim of this experimental study was to investigate the accumulation of three 131 I- labeled anti-EGFR antibodies - panitumumab, cetuximab and nimotuzumab using a kidney model in vitro, and compare it with renal uptake of the natural peptide ligand EGFR which was..