title: Radiopharmaceutical chemistry of targeted radiotherapeutics, part 1: effects of solvent on the degradation of radiohalogenation precursors by 211At alpha-particles.
abstract: The high energy and short range of alpha-particles make them attractive for targeted radiotherapy. However, these properties can be problematic when the production of high activity levels of alpha-particle-emitting radiotherapeutics is required. For example, difficulties were encountered in the production of N-succinimidyl 3-[211At]-astatobenzoate (SAB), when 370-MBq doses of 211At-labeled antibody were required. The purpose of this study was to investigate a potential cause of this behavior--radiolytic degradation of the radiohalogenation precursor.
  
  
  METHODS
  Both N-succinimidyl 3-(tri-n-butylstannyl)benzoate (BuSTB) and N-succinimidyl 3-trimethylstannylbenzoate (MeSTB) were incubated with various 211At time-activity combinations such that the radiation dose received by the reaction medium ranged from about 0 to 20,000 Gy. Studies were performed using chloroform, methanol, and benzene as the solvent, and both at neutral pH and at a pH of approximately 5.5, as used in SAB synthesis. The fraction of tin precursor remaining and the generation of unlabeled byproducts were determined from high-performance liquid chromatograms and then plotted against radiation dose.
  
  
  RESULTS
  Extensive radiolytic decomposition of BuSTB and MeSTB was observed in chloroform, with 50% degradation taking place even at doses below 500 Gy. Formation of a byproduct, most likely N-succinimidyl 3-chlorobenzoate, increased with radiation dose. A greater degree of stability was seen in both methanol and benzene, with more than 85% of the precursor remaining at 3,500 Gy. No cold byproducts were observed with either solvent.
  
  
  CONCLUSIONS
  The nature of the solvent profoundly influences the ability to synthesize high activity levels of SAB and possibly other 211At-labeled radiopharmaceuticals.
authors.affiliation: Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Oscar R
authors.initials: OR
authors.lastname: Pozzi
authors.forename: Michael R
authors.initials: MR
authors.lastname: Zalutsky
mesh_terms: D000512:Alpha Particles; D001246:Astatine / Q000737:chemistry*; D006219:Halogens / Q000737:chemistry*; D016499:Radioimmunotherapy / Q000379:methods*; D019275:Radiopharmaceuticals / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry*
chemical_list: D006219:Halogens; D019275:Radiopharmaceuticals; D012997:Solvents; D001246:Astatine