title: Sequential radioimmunotherapy with 177Lu- and 211At-labeled monoclonal antibody BR96 in a syngeneic rat colon carcinoma model.
abstract: Alpha-particle emitters, such as astatine-211 (211At), are generally considered suitable for the treatment of small cell clusters due to their short path length, while beta-particle emitters, for example, Lutetium-177 (177Lu), have a longer path length and are considered better for small, established tumors. A combination of such radionuclides may be successful in regimens of radioimmunotherapy. In this study, rats were treated by sequential administration of first a 177Lu-labeled antibody, followed by a 211At-labeled antibody 25 days later.
  
  
  METHODS
  Rats bearing solid colon carcinoma tumors were treated with 400 MBq/kg body weight 177Lu-BR96. After 25 days, three groups of animals were given either 5 or 10 MBq/kg body weight of 211At-BR96 simultaneously with or without a blocking agent reducing halogen uptake in normal tissues. Control animals were not given any 211At-BR96. Myelotoxicity, body weight, tumor size, and development of metastases were monitored for 120 days.
  
  
  RESULTS
  Tumors were undetectable in 90% of the animals on day 25, independent of treatment. Additional treatment with 211At-labeled antibodies did not reduce the proportion of animals developing metastases. The rats suffered from reversible myelotoxicity after treatment.
  
  
  CONCLUSIONS
  Sequential administration of 177Lu-BR96 and 211At-BR96 resulted in tolerable toxicity providing halogen blocking but did not enhance the therapeutic effect.
authors: 1 Department of Oncology and Pathology, Lund University , Lund, Sweden .
authors: Sophie E
authors: SE
authors: Eriksson
authors: Erika
authors: E
authors: Elgström
authors: Tom
authors: T
authors: Bäck
authors: Tomas
authors: T
authors: Ohlsson
authors: Holger
authors: H
authors: Jensen
authors: Rune
authors: R
authors: Nilsson
authors: Sture
authors: S
authors: Lindegren
authors: Jan
authors: J
authors: Tennvall
mesh_terms: D000512:Alpha Particles; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D001246:Astatine / Q000008:administration & dosage*; D003110:Colonic Neoplasms / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy*; D004195:Disease Models, Animal; D006801:Humans; D008187:Lutetium / Q000008:administration & dosage*; D016499:Radioimmunotherapy / Q000379:methods*; D011868:Radioisotopes / Q000008:administration & dosage*; D019275:Radiopharmaceuticals / Q000008:administration & dosage; D051381:Rats
chemical_list: D000911:Antibodies, Monoclonal; C507851:BR96 monoclonal antibody; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D008187:Lutetium; D001246:Astatine
keywords: astatine-211; lutetium-177; radioimmunotherapy; targeted alpha therapy