title: In vitro evaluation of the astatinated chimeric monoclonal antibody U36, a potential candidate for treatment of head and neck squamous cell carcinoma.
abstract: OBJECTIVE
  The purpose of this study was to analyse the properties of the astatinated chimeric MAb (cMAb) U36 as a conjugate to selectively target and eradicate head and neck squamous cell carcinoma (HNSCC).
  
  
  METHODS
  cMAb U36 was labelled with 211At via the linker N-succinimidyl 4-(trimethylstannyl)benzoate (SPMB). The quality of the conjugate was extensively evaluated for binding and internalisation capacity, and compared with 125I-SPMB-cMAb U36. The cellular toxicity of the astatinated conjugate was assessed in two types of in vitro growth assay and compared with 131I-labelled cMAb U36 (directly labelled).
  
  
  RESULTS
  Comparisons between 211At-cMAb U36 and 125I-cMAb U36 demonstrated an optimal functional capacity of the labelled products. Immunoreactivity and affinity assays showed high immunoreactive fractions (>93%), and an affinity in good agreement between the astatinated and iodinated antibodies. For both conjugates, specific binding to HNSCC cells could be demonstrated, as well as some internalisation. Retention of the astatinated conjugate was just slightly lower than for the iodinated conjugate and still reasonable for therapeutic use (31+/-2% vs 42.6+/-1.0% at 22 h), demonstrating no adverse effects from astatination of the antibody. Studies on cellular toxicity demonstrated a dose-dependent and antigen-specific cellular toxicity for 211At-cMAb U36, with about 10% cell survival at 50 decays per cell. The 131I-labelled conjugate was not as efficient, with a surviving cell fraction of about 50% at 55 decays per cell.
  
  
  CONCLUSIONS
  These results indicate that 211At-cMAb U36 might be a promising future candidate for eradicating HNSCC micrometastases in vivo.
authors: Unit of Otolaryngology and Head & Neck Surgery, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden. Marika.Nestor@bms.uu.se
authors: M
authors: M
authors: Nestor
authors: M
authors: M
authors: Persson
authors: G A M S
authors: GA
authors: van Dongen
authors: H J
authors: HJ
authors: Jensen
authors: H
authors: H
authors: Lundqvist
authors: M
authors: M
authors: Anniko
authors: V
authors: V
authors: Tolmachev
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001246:Astatine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects*; D004353:Drug Evaluation, Preclinical; D005240:Feasibility Studies; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D016499:Radioimmunotherapy / Q000379:methods
chemical_list: D000911:Antibodies, Monoclonal; D001246:Astatine