title: Radiotoxicity of systematically administered [211At]astatide in B6C3F1 and BALB/c (nu/nu) mice: a long-term survival study with histologic analysis.
abstract: OBJECTIVE
  The present study undertook to establish the dose (LD) of systematically administered (via tail vein) sodium [211At]astatide that would kill 10% (LD10) of exposed animals in two mouse models and to evaluate the resulting histologic lesions.
  
  
  METHODS
  Three dose escalation experiments were carried out using groups of 10 3- to 4-week-old, 20 +/- 2 g B6C3F1 mice, and one dose escalation experiment was carried out with groups of 10 4- to 6-week-old, 22 +/- 2 g BALB/c (nu/nu) mice. All animals were weighed daily and checked twice daily for general health; autopsies were performed within 12 h of death.
  
  
  RESULTS
  The LD10 (95% confidence interval) level of free [211At]astatide at 360 days was 15.1 microCi (5.2-19.1 microCi) in B6C3F1 mice and was associated with a 37.8% weight difference from saline controls (p < 0.001). In the BALB/c (nu/nu) mice, the LD10 at 360 days was 7.7 microCi (0-14.2 microCi), while a dose of 10 microCi (0.42 microCi g(-1)) was associated with a 9.44% weight difference vs. saline controls (p < 0.05). Exclusive of the well-known effects on thyroid, [211At]astatide activity levels were associated with severe bone marrow depression, testicular atrophy, focal alopecia, and nuclear atypia of the epidermoid mucosa of the fore-stomach in the B6C3F1 mice; at activity levels approximating LD10 at 360 days, mild changes in the heart, liver, stomach, and spleen were observed. For BALB/c (nu/nu) mice, administration of 10 microCi was associated at autopsy with mild histologic lesions in the heart, stomach, liver, and spleen.
  
  
  CONCLUSIONS
  These studies provide a basis for the design of further investigations of [211At]-labeled compounds as therapeutic agents.
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, NC, 27710, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: McLendon
authors.forename: G E
authors.initials: GE
authors.lastname: Archer
authors.forename: P K
authors.initials: PK
authors.lastname: Garg
authors.forename: D D
authors.initials: DD
authors.lastname: Bigner
authors.forename: M R
authors.initials: MR
authors.lastname: Zalutsky
mesh_terms: D000818:Animals; D001246:Astatine / Q000633:toxicity*; D001853:Bone Marrow / Q000528:radiation effects; D006321:Heart / Q000528:radiation effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D013270:Stomach / Q000473:pathology / Q000528:radiation effects; D013737:Testis / Q000473:pathology / Q000528:radiation effects; D015430:Weight Gain / Q000528:radiation effects
chemical_list: D001246:Astatine