title: Preclinical evaluation of radiolabelled nimotuzumab, a promising monoclonal antibody targeting the epidermal growth factor receptor.
abstract: BACKGROUND
  Radiolabelled monoclonal antibodies with affinity towards tumour-associated antigens may enhance the efficacy of cancer treatment with targeted radiotherapy. The humanized antibody nimotuzumab represents a promising vector to deliver radioactivity to tumours overexpressing epidermal growth factor receptor type 1 (ErbB1). We analysed the effect of radiolabelling nimotuzumab on its uptake in cancer cells and its biodistribution profile in preclinical experiments.
  
  
  METHODS
  Nimotuzumab was labelled with (131) I by oxidative iodination and with (177) Lu using nimotuzumab conjugates with two different chelators (DTPA and DOTA) and two different spacers (p-SCN-Bn and NHS). For the receptor studies, two cell lines (HaCaT and A431) were used. Biodistribution studies were performed in male Wistar rats.
  
  
  RESULTS
  The choice of radiolabel and the manner of its attachment to nimotuzumab had little effect on the internalization of the antibody into ErbB1-expressing cell lines. However, the type of radiolabel, the way in which it was attached to nimotuzumab and the radiolabelling procedure, significantly affected the blood clearance, liver uptake and liver persistence of radiolabelled nimotuzumab. (131) I-nimotuzumab had the longest elimination half-life and the lowest radioactivity uptake in the liver. (177) Lu-labelled nimotuzumab exhibited a shorter elimination half-life, high radioactivity and long-term retention in the liver.
authors.affiliation: Department of Pharmacology and Toxicology, Charles University in Prague, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Barta
authors.forename: Alice
authors.initials: A
authors.lastname: Laznickova
authors.forename: Milan
authors.initials: M
authors.lastname: Laznicek
authors.forename: Denis Rolando Beckford
authors.initials: DR
authors.lastname: Vera
authors.forename: Milos
authors.initials: M
authors.lastname: Beran
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007457:Iodine Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D007553:Isotope Labeling; D008187:Lutetium / Q000737:chemistry / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D014018:Tissue Distribution
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D008187:Lutetium; C501466:nimotuzumab
keywords: 131I; 177Lu; EGFR; nimotuzumab; preclinical biodistribution; radiopharmaceutical