title: Direct technetium-99m labeling of three anticancer monoclonal antibodies: stability, pharmacokinetics and imaging.
abstract: Monoclonal antibodies (MAbs) directly labeled with 99mTc have been used in a number of clinical immunoscintigraphic investigations. Three anti-cancer MAbs were radiolabeled with 99mTc using a reduction-mediated technique. The stability, biodistribution and in vivo pharmacokinetics were assessed and compared with the same antibodies labeled with 125I.
  
  
  METHODS
  Immunoreactivity data were obtained by ELISA and RIA. Homogeneity and stability of radiolabeled antibodies (in vitro and in vivo) were measured by size-exclusion, fast protein liquid chromatography and SDS-PAGE. Pre-clinical, in vivo investigations utilized the nude mouse/HEp2 xenograft model, and clinical imaging and pharmacokinetic data were obtained from patients with confirmed or suspected lesions.
  
  
  RESULTS
  Both 99mTc- and 125I-labeled antibodies were shown to be homogeneous and stable, although 99mTc-labeled antibody fragments were detected by SDS-PAGE. Pharmacokinetic studies in patients revealed a significant difference in the clearance rates between 99mTc- and 125I-labeled antibodies, with those labeled with 99mTc having a shorter biological half-life, indicating that the 99mTc-labeled antibodies may be less stable than the iodinated ones. Nevertheless, specific tumor localization was successfully demonstrated in nude mice bearing a human tumor xenograft using 125I- and 99mTc-labeled H17E2 antibody. Furthermore, in the clinic, using 99mTc-labeled HMFG1 and 1A3, successful imaging was achieved in 12 out of 19 patients with lesions for which these antibodies were specific.
  
  
  CONCLUSIONS
  Anticancer MAbs radiolabelled using this reduction-mediated technique are suitable agents for clinical, immunoscintigraphic investigations.
authors.affiliation: Department of Clinical Oncology, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
authors.forename: C S
authors.initials: CS
authors.lastname: Gooden
authors.forename: D E
authors.initials: DE
authors.lastname: Snook
authors.forename: A
authors.initials: A
authors.lastname: Maraveyas
authors.forename: G
authors.initials: G
authors.lastname: Rowlinson-Busza
authors.forename: A M
authors.initials: AM
authors.lastname: Peters
authors.forename: A A
authors.initials: AA
authors.lastname: Epenetos
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000276:immunology; D016719:Radioimmunodetection; D013667:Technetium / Q000493:pharmacokinetics
chemical_list: D000911:Antibodies, Monoclonal; C106201:H17E2 monoclonal antibody; D007457:Iodine Radioisotopes; D013667:Technetium