title: A Phase 1, Open-Label Study of the Biodistribution, Pharmacokinetics, and Dosimetry of 223Ra-Dichloride in Patients with Hormone-Refractory Prostate Cancer and Skeletal Metastases.
abstract: The aim of this single-site, open-label clinical trial was to determine the biodistribution, pharmacokinetics, absorbed doses, and safety from 2 sequential weight-based administrations of (223)Ra-dichloride in patients with bone metastases due to castration-refractory prostate cancer.
  
  
  METHODS
  Six patients received 2 intravenous injections of (223)Ra-dichloride, 6 wk apart, at 100 kBq/kg of whole-body weight. The pharmacokinetics and biodistribution as a function of time were determined, and dosimetry was performed for a range of organs including bone surfaces, red marrow, kidneys, gut, and whole body using scintigraphic imaging; external counting; and blood, fecal, and urine collection. Safety was assessed from adverse events.
  
  
  RESULTS
  The injected activity cleared rapidly from blood, with 1.1% remaining at 24 h. The main route of excretion was via the gut, although no significant toxicity was reported. Most of the administered activity was taken up rapidly into bone (61% at 4 h). The range of absorbed doses delivered to the bone surfaces from α emissions was 2,331-13,118 mGy/MBq. The ranges of absorbed doses delivered to the red marrow were 177-994 and 1-5 mGy/MBq from activity on the bone surfaces and from activity in the blood, respectively. No activity-limiting toxicity was observed at these levels of administration. The absorbed doses from the second treatment were correlated significantly with the first for a combination of the whole body, bone surfaces, kidneys, and liver.
  
  
  CONCLUSIONS
  A wide range of interpatient absorbed doses was delivered to normal organs. Intrapatient absorbed doses were significantly correlated between the 2 administrations for any given patient. The lack of gastrointestinal toxicity is likely due to the low absorbed doses delivered to the gut wall from the gut contents. The lack of adverse myelotoxicity implies that the absorbed dose delivered from the circulating activity may be a more relevant guide to the potential for marrow toxicity than that due to activity on the bone surfaces.
authors.affiliation: Joint Department of Physics, Royal Marsden Hospital and Institute of Cancer Research, Sutton, Surrey, United Kingdom sarah.chittenden@icr.ac.uk.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Chittenden
authors.affiliation: Department of Radiation Physics, Radionuklidcentralen, Skåne University Hospital Lund, Lund, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Hindorf
authors.affiliation: Department of Urology, Royal Marsden Hospital, Sutton, Surrey, United Kingdom; and.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Parker
authors.affiliation: Department of Nuclear Medicine, Guy's Hospital, London, United Kingdom.
authors.forename: Valerie J
authors.initials: VJ
authors.lastname: Lewington
authors.affiliation: Joint Department of Physics, Royal Marsden Hospital and Institute of Cancer Research, Sutton, Surrey, United Kingdom.
authors.forename: Brenda E
authors.initials: BE
authors.lastname: Pratt
authors.affiliation: Department of Urology, Royal Marsden Hospital, Sutton, Surrey, United Kingdom; and.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Johnson
authors.affiliation: Joint Department of Physics, Royal Marsden Hospital and Institute of Cancer Research, Sutton, Surrey, United Kingdom.
authors.forename: Glenn D
authors.initials: GD
authors.lastname: Flux
mesh_terms: D000368:Aged; D001822:Body Burden; D001859:Bone Neoplasms / Q000378:metabolism* / Q000532:radiotherapy / Q000556:secondary*; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009928:Organ Specificity; D064129:Prostatic Neoplasms, Castration-Resistant / Q000378:metabolism* / Q000532:radiotherapy; D011829:Radiation Dosage; D011868:Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011883:Radium / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014018:Tissue Distribution; D016896:Treatment Outcome; D014915:Whole-Body Counting
chemical_list: D011868:Radioisotopes; D019275:Radiopharmaceuticals; C581106:radium Ra 223 dichloride; D011883:Radium
keywords: 223Ra; biodistribution; dosimetry; molecular radiotherapy; α-emitter