title: Therapeutic efficacy of astatine-211-labeled trastuzumab on radioresistant SKOV-3 tumors in nude mice.
abstract: OBJECTIVE
  To investigate the potential use of astatine-211 (211At)-labeled trastuzumab for the treatment of HER-2-positive, radioresistant ovarian carcinoma.
  
  
  METHODS
  Four-week-old nude mice were inoculated intraperitoneally with 5 . 10(6) SKOV-3 cells in 0.4 mL saline on Day 0. The endpoint was the total tumor weight in each mouse on Day 63. Three experiments were performed in which the response to single-dose and fractionated treatment with unlabeled and 211At-labeled antibody was evaluated.
  
  
  RESULTS
  Experiment 1 showed, for the same total amount of trastuzumab, a dose-response relationship between 211At activity (0-400 kBq on Day 7) and therapeutic efficacy (p = 0.001). The effect of varying the amount of unlabeled trastuzumab was studied in Experiment 2. All mice, except for the controls, received 400 kBq 211At-trastuzumab, and different groups received 5, 50, or 500 microg trastuzumab on Day 7. The increase from 5 to 50 microg trastuzumab reduced the tumors by 78% in weight. No tumors were present in mice given 500 microg trastuzumab. In Experiment 3, the effect of a fractionated treatment regimen was studied. Mice that received 100 kBq 211At-trastuzumab on Days 7 and 8 had a 42% smaller tumor burden than did controls. Groups of mice injected with 200 + 100 kBq on Days 7 and 21 and mice injected with 100 kBq on Days 7, 8, and 21 both had 24% less tumor weight than the corresponding controls.
  
  
  CONCLUSIONS
  The combination of 500 microg trastuzumab and 400 kBq 211At-trastuzumab had the greatest effect, with complete eradication of the tumors in this nude mouse model.
authors.affiliation: Department of Radiation Physics, Sahlgrenska Academy at Göteborg University, Göteborg, Sweden. stig.palm@radfys.gu.se
authors.forename: Stig
authors.initials: S
authors.lastname: Palm
authors.forename: Tom
authors.initials: T
authors.lastname: Bäck
authors.forename: Ingela
authors.initials: I
authors.lastname: Claesson
authors.forename: Anna
authors.initials: A
authors.lastname: Danielsson
authors.forename: Jörgen
authors.initials: J
authors.lastname: Elgqvist
authors.forename: Sofia
authors.initials: S
authors.lastname: Frost
authors.forename: Ragnar
authors.initials: R
authors.lastname: Hultborn
authors.forename: Holger
authors.initials: H
authors.lastname: Jensen
authors.forename: Sture
authors.initials: S
authors.lastname: Lindegren
authors.forename: Lars
authors.initials: L
authors.lastname: Jacobsson
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001246:Astatine / Q000008:administration & dosage / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000473:pathology / Q000532:radiotherapy*; D011836:Radiation Tolerance; D016499:Radioimmunotherapy / Q000379:methods*; D011879:Radiotherapy Dosage; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D001246:Astatine; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab