title: Comparison of therapeutic efficacy and biodistribution of 213Bi- and 211At-labeled monoclonal antibody MX35 in an ovarian cancer model.
abstract: BACKGROUND
  The purpose of this study was to compare the therapeutic efficacy and biodistribution of the monoclonal antibody MX35 labeled with either (213)Bi or (211)At, both α-emitters, in an ovarian cancer model.
  
  
  METHODS
  One hundred female nude BALB/c (nu/nu) mice were inoculated intraperitoneally with human ovarian cancer cells (OVCAR-3). Two weeks later, 40 of these mice were injected intraperitoneally with ~2.7 MBq of (213)Bi-MX35 (n=20) or ~0.44 MBq of (211)At-MX35 (n=20). Four weeks after inoculation, 40 new OVCAR-3-inoculated mice were injected with the same activities of (213)Bi-MX35 (n=20) or (211)At-MX35 (n=20). Presence of tumors and ascites was investigated 8 weeks after therapy. Biodistributions of intraperitoneally injected (213)Bi-MX35 and (211)At-MX35 were studied in tumor-free nude BALB/c (nu/nu) mice (n=16).
  
  
  RESULTS
  The animals injected with (213)Bi-MX35 or (211)At-MX35 2 weeks after cell inoculation had tumor-free fractions (TFFs) of 0.60 and 0.90, respectively. The untreated reference group had a TFF of 0.20. The groups treated with (213)Bi-MX35 or (211)At-MX35 4 weeks after inoculation both had TFFs of 0.25, and the reference animals all exhibited evidence of disease. The biodistributions of (213)Bi-MX35 and (211)At-MX35 were very similar to each other and displayed no alarming activity levels in the investigated organs.
  
  
  CONCLUSIONS
  Micrometastatic growth of an ovarian cancer cell line was reduced in nude mice after treatment with (213)Bi-MX35or (211)At-MX35. Treatment with (211)At-MX35 provided a non-significantly better result for the chosen activity levels. The radiolabeled MX35 did not accumulate to a high extent in the investigated organs. No considerable signs of toxicity were observed.
authors.affiliation: Department of Radiation Physics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. anna.gustafsson@radfys.gu.se
authors.forename: Anna M E
authors.initials: AM
authors.lastname: Gustafsson
authors.forename: Tom
authors.initials: T
authors.lastname: Bäck
authors.forename: Jörgen
authors.initials: J
authors.lastname: Elgqvist
authors.forename: Lars
authors.initials: L
authors.lastname: Jacobsson
authors.forename: Ragnar
authors.initials: R
authors.lastname: Hultborn
authors.forename: Per
authors.initials: P
authors.lastname: Albertsson
authors.forename: Alfred
authors.initials: A
authors.lastname: Morgenstern
authors.forename: Frank
authors.initials: F
authors.lastname: Bruchertseifer
authors.forename: Holger
authors.initials: H
authors.lastname: Jensen
authors.forename: Sture
authors.initials: S
authors.lastname: Lindegren
mesh_terms: D000512:Alpha Particles / Q000627:therapeutic use; D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental; D009942:Organometallic Compounds / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000532:radiotherapy; D011868:Radioisotopes / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014018:Tissue Distribution; D016896:Treatment Outcome
chemical_list: C507514:211At-labeled monoclonal antibody MX35; C528533:213Bi-cDTPA-9.2.27 monoclonal antibody; D000911:Antibodies, Monoclonal; D009942:Organometallic Compounds; D011868:Radioisotopes