title: Radiopharmaceutical chemistry of targeted radiotherapeutics, part 4: Strategies for211At labeling at high activities and radiation doses of211At α-particles.
abstract: BACKGROUND
  Alpha particles are radiation of high energy and short range, properties that can lead to radiolysis-mediated complications in labeling chemistry at the high radioactivity levels required for clinical application. In previous papers in this series, we have shown that radiation dose has a profound effect on the astatine species that are present in the labeling reaction and their suitability for the synthesis of N-succinimidyl 3-[211At]astatobenzoate. The purpose of this study was to evaluate the effects of adding N-chlorosuccinimide (NCS) to the methanol solution used for initial isolation of211At after distillation, a process referred to as211At stabilization, on211At chemistry after exposure to high radiation doses.
  
  
  METHODS
  High performance liquid chromatography was used to evaluate the distribution of211At species present in methanol in the 500-65,000Gy radiation dose range and the synthesis of SAB from N-succinimidyl 3-(tri-n-butylstannyl)benzoate in the 500-120,000Gy radiation dose range using different211At timeactivity combinations under conditions with/without211At stabilization.
  
  
  RESULTS
  In the absence of NCS stabilization, a reduced form of astatine, At(2), increased with increasing radiation dose, accounting for about half the total activity by about 15,000Gy, while with stabilization, At(2) accounted for <10% of211At activity even at doses >60,000Gy. SAB yields without stabilization rapidly declined with increasing dose, falling to ~20% at about 5000Gy while with stabilization, yields >80% were obtained with211At solutions stored for more than 23h and receiving radiation doses >100,000Gy.
  
  
  CONCLUSIONS
  Adding NCS to the methanol solution used for initial isolation of211At is a promising strategy for countering the deleterious effects of radiolysis on211At chemistry.
  
  
  CONCLUSIONS
  This strategy could facilitate the ability to perform211At labeling at sites remote from its production and at the high activity levels required for clinical applications.
authors.affiliation: Department of Radiology, Duke University Medical Center, Durham, NC, 27710, USA. Electronic address: oscarpozzi@hotmail.com.
authors.forename: Oscar R
authors.initials: OR
authors.lastname: Pozzi
authors.affiliation: Department of Radiology, Duke University Medical Center, Durham, NC, 27710, USA. Electronic address: zalut001@mc.duke.edu.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Zalutsky
mesh_terms: D000512:Alpha Particles / Q000627:therapeutic use*; D001246:Astatine / Q000737:chemistry* / Q000627:therapeutic use*; D007553:Isotope Labeling; D011829:Radiation Dosage; D011854:Radiochemistry; D019275:Radiopharmaceuticals / Q000737:chemistry* / Q000627:therapeutic use*
chemical_list: D019275:Radiopharmaceuticals; D001246:Astatine
keywords: (211)At; Radiolysis; Radionuclide therapy; Targeted radiotherapy; α-particles