title: Treatment of experimental pancreatic cancer with 213-Bismuth-labeled chimeric antibody to single-strand DNA.
abstract: BACKGROUND
  Novel approaches to treatment of pancreatic cancer (PCa) are urgently needed. A chimeric monoclonal antibody (mAb) chTNT3 binds to single-strand DNA (ssDNA) and RNA released from the non-viable cells in fast growing tumors. Here the authors investigated whether radioimmunotherapy (RIT) using chTNT3 mAb radiolabeled with 213-Bismuth ((213)Bi) could be effective in treatment of experimental PCa.
  
  
  METHODS
  Two human PCa cell lines, Panc1 and MiaPaCa-2, were used for in vitro experiments. The xenografts in mice were established using MiaPaCa-2 cells. Therapy compared (213)Bi-chTNT3 (700 μCi) to gemcitabine or cisplatin, untreated controls and 'cold' chTNT3.
  
  
  RESULTS
  RIT abrogated the tumors growth while tumors in control groups grew aggressively. Chemotherapy was less effective than RIT and toxic to mice while RIT did not have any side effects.
  
  
  CONCLUSIONS
  RIT with (213)Bi-chTNT3 was safe and effective in the treatment of experimental PCa in comparison with chemotherapy. This makes α-RIT targeting ssDNA a promising modality for further development.
authors.affiliation: Department of Radiology, Albert Einstein College of Medicine, 1695A Eastchester Rd. Bronx, NY 10461, USA.
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Bryan
authors.forename: Zewei
authors.initials: Z
authors.lastname: Jiang
authors.forename: Thomas
authors.initials: T
authors.lastname: Jandl
authors.forename: Julius
authors.initials: J
authors.lastname: Strauss
authors.forename: Wade
authors.initials: W
authors.lastname: Koba
authors.forename: Chukwuemeka
authors.initials: C
authors.lastname: Onyedika
authors.forename: Alfred
authors.initials: A
authors.lastname: Morgenstern
authors.forename: Frank
authors.initials: F
authors.lastname: Bruchertseifer
authors.forename: Alan L
authors.initials: AL
authors.lastname: Epstein
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Dadachova
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001729:Bismuth / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use; D004247:DNA / Q000378:metabolism; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000628:therapy*; D016499:Radioimmunotherapy / Q000009:adverse effects / Q000379:methods*; D011868:Radioisotopes / Q000008:administration & dosage; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D011868:Radioisotopes; D003841:Deoxycytidine; D004247:DNA; D002945:Cisplatin; D001729:Bismuth; D000093542:Gemcitabine
keywords: 213-Bismuth; cisplatin; gemcitabine; intracellular antigens; pancreatic cancer; radioimmunotherapy; single-strand DNA