Modification of antibody fragments and their radiolabeling by unconventional positron emitters and biological testing for PET diagnostics

Charles University, Faculty of Pharmacy in Hradec Králové Department of Department of Pharmacology and Toxycology Candidate Adam Cepa, MSc. Supervisor Prof. PharmDr. Ing. Milan Laznicek, CSc. Title of Doctoral Thesis Modification of antibody fragments and their radiolabeling by unconventional positron emitters and biological testing for PET diagnostics Special oncology diagnostics require new types of selective radiopharmaceuticals, especially those that are suitable for molecular PET imaging and therapy, respectively, teranostics. The aim of this work is to present a new target radiopharmaceutical for immunoPET diagnosis and therapy based on the monoclonal antibody IgG M75 directed to human carbonic anhydrase IX, nimotuzumab (hR3) target epidermal growth factor receptor (EGFR) and one of the bombesin derivatives (BBN) repeats. These molecules were labeled with radionuclides 64Cu (t1/2 12.70 hours), 61Cu (t1/2 3.33 hours), 68Ga (t1/2 68 min), 177Lu (t1/2 6.71 days). These potential radiopharmaceuticals were evaluated in vitro and in vivo. The IgG M75 antibody and its scFv-Fc M75 fragment were prepared by the genetic modification were conjugated to a specific chelator specific phosphinate (PHS) and radiolabeled by the radionuclides 61,64Cu. The stability of the labeled conjugate was tested in human..