title: Preparation and biological evaluation of (177)Lu conjugated PR81 for radioimmunotherapy of breast cancer.
abstract: OBJECTIVE
  PR81 is a monoclonal antibody that binds with high affinity to MUC1 antigen that is over expressed in 80% of breast cancers. In this study, we developed a method for indirect labeling of PR81 with lutetium-177 and performed all preclinical qualifications in production of a biologic agent for radioimmunotherapy of breast cancer.
  
  
  METHODS
  The radiochemical purity and in vitro stability of (177)Lu labeled PR81 was determined by instant thin layer chromatography. The immunoreactivity and cell toxicity of the complex were tested on MCF7 cell line. The biodistribution and scintigraphy studies were performed in BALB/c mice with breast tumor.
  
  
  RESULTS
  The radiochemical purity was 91.2±3.8% after 2 h. The in vitro stabilities in phosphate buffer and human blood serum were 83.1±3.4% and 76.2±3.6% at 96 h, respectively. The immunoreactivity of the complex was 83.4±2.4%. The cell toxicity study showed that the complex inhibited 85.2±3.4% growth of MCF7 cells at a concentration of 2500 ng/ml after 96 h. The biodistribution and scintigraphy studies showed the accumulation of the complex at the site of tumors with high sensitivity and specificity.
  
  
  CONCLUSIONS
  The results showed that one may consider (177)Lu-DOTA-PR81 as a potential radiopharmaceutical for therapy of human breast cancer, which needs further investigations.
authors.affiliation: Department of Biology, Faculty of Sciences, Zanjan Branch, Islamic Azad University, Zanjan 45156-58145, Iran. saloutim@yahoo.com
authors.forename: Mojtaba
authors.initials: M
authors.lastname: Salouti
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Babaei
authors.forename: Hossein
authors.initials: H
authors.lastname: Rajabi
authors.forename: Mohammad javad
authors.initials: Mj
authors.lastname: Rasaee
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology / Q000378:metabolism / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D005260:Female; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D006801:Humans; D008187:Lutetium / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D011786:Quality Control; D016719:Radioimmunodetection; D016499:Radioimmunotherapy / Q000379:methods*; D011868:Radioisotopes / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D006573:Heterocyclic Compounds, 1-Ring; D011868:Radioisotopes; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D008187:Lutetium