Labeling Monoclonal Antibody with α-emitting 211At at High Activity Levels via a Tin Precursor

Cancer Biother Radiopharm. 2020 Sep;35(7):511-519. doi: 10.1089/cbr.2019.3204. Epub 2020 Feb 28.


Background: In a previous clinical study, the authors evaluated the potential of antitenascin C monoclonal antibody (mAb) 81C6 labeled with 211At via the prosthetic agent N-succinimidyl 3-[211At]astatobenzoate (SAB) for the treatment of primary brain tumors. Although encouraging results were obtained, labeling chemistry failed while attempting to escalate the dose to 370 MBq. The goal of the current study was to develop a revised procedure less susceptible to radiolysis-mediated effects on 211At labeling that would be suitable for use at higher activity levels of this α-emitter. Materials and Methods: Addition of N-chlorosuccinimide to the methanol used to remove the 211At from the cryotrap after bismuth target distillation was done to thwart radiolytic decomposition of reactive 211At and the tin precursor. A series of 11 reactions were performed to produce SAB at initial 211At activity levels of 0.31-2.74 GBq from 50 μg of N-succinimidyl 3-trimethylstannylbenzoate (Me-STB), which was then reacted with murine 81C6 mAb without purification of the SAB intermediate. Radiochemical purity, immunoreactive fraction, sterility, and apyrogenicity of the 211At-labeled 81C6 preparations were evaluated. Results: Murine 81C6 mAb was successfully labeled with 211At using these revised procedures with improved radiochemical yields and decreased overall synthesis time compared with the original clinical labeling procedure. Conclusions: With 2.74 GBq of 211At, it was possible to produce 1.0 GBq of 211At-labeled 81C6 with an immunoreactive fraction of 92%. These revised procedures permit production of 211At-labeled mAbs suitable for use at clinically relevant activity levels.

Keywords: Astatine-211; monoclonal antibodies; radioimmunotherapy; targeted radiotherapy; α-particles.

MeSH terms

  • Alpha Particles / therapeutic use
  • Animals
  • Antibodies, Monoclonal / chemistry*
  • Antibodies, Monoclonal / isolation & purification
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / therapeutic use
  • Astatine / chemistry*
  • Astatine / isolation & purification
  • Astatine / pharmacokinetics
  • Astatine / therapeutic use
  • Benzoates / chemistry
  • Brain Neoplasms / immunology
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy*
  • Cell Line, Tumor
  • Glioma / immunology
  • Glioma / pathology
  • Glioma / therapy*
  • Humans
  • Isotope Labeling / methods*
  • Mice
  • Radioimmunotherapy / methods
  • Tissue Distribution
  • Trimethyltin Compounds / chemistry
  • Xenograft Model Antitumor Assays


  • Antibodies, Monoclonal
  • Astatine-211
  • Benzoates
  • Trimethyltin Compounds
  • N-succinimidyl 3-(trimethylstannyl)benzoate
  • Astatine