title: Extracorporeal adsorption therapy: a method to improve targeted radiation delivered by radiometal-labeled monoclonal antibodies.
abstract: OBJECTIVE
  Radiolabeled anti-CD20 antibodies have demonstrated impressive efficacy in the treatment of relapsed non-Hodgkin's lymphoma. However, the amount of radiation that can be delivered to eradicate the malignancy is limited by toxicity to normal organs. We examined an "extracorporeal adsorption therapy" (ECAT) method to remove circulating unbound radioimmunoconjugate and improve the ratios of radiation delivered to B-cells in a macaque model.
  
  
  METHODS
  ECAT was applied with an avidin-agarose column 24 hours after an injection of (111)In- or (177)Lu-DOTA-biotin-rituximab (anti-CD20 antibody) to normal macaques. Two (2) animals were studied in initial blood clearance studies, and 6 additional animals were evaluated in subsequent detailed biodistribution experiments. After the injection of (111)In- or (177)Lu-antibody, 3 animals underwent ECAT circulating one volume/hour while 3 served as controls. Serial blood, marrow, and lymph node samples, gamma-camera images, and necropsy tissues were obtained to estimate radiation-absorbed doses in organs of interest.
  
  
  RESULTS
  Optimal blood clearance (98%) was achieved by performing ECAT at a flow rate of one blood volume/hour. Radiation doses to normal organs were reduced with ECAT in kidney (49% +/- 12%), liver (42% +/- 10%), lungs (60% +/- 6%), total body (51% +/- 16%), marrow (50% +/- 15%), spleen (38% +/- 10%), and lymph nodes (19% +/- 3%). Despite dose reduction in both target and nontarget tissues, therapeutic ratios were significantly higher in animals treated with ECAT (20% higher for spleen:kidney and 60% for lymph node:kidney), compared to controls.
  
  
  CONCLUSIONS
  ECAT is a safe, feasible, and effective method to remove unbound radioimmunoconjugates from the bloodstream and reduce the nonspecific radiation exposure of normal tissues.
authors.affiliation: Department of Pediatrics, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Eneida R
authors.initials: ER
authors.lastname: Nemecek
authors.forename: Damian J
authors.initials: DJ
authors.lastname: Green
authors.forename: Darrell R
authors.initials: DR
authors.lastname: Fisher
authors.forename: John M
authors.initials: JM
authors.lastname: Pagel
authors.forename: Yukang
authors.initials: Y
authors.lastname: Lin
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Gopal
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Durack
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Rajendran
authors.forename: D Scott
authors.initials: DS
authors.lastname: Wilbur
authors.forename: Rune
authors.initials: R
authors.lastname: Nilsson
authors.forename: Bengt
authors.initials: B
authors.lastname: Sandberg
authors.forename: Oliver W
authors.initials: OW
authors.lastname: Press
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology* / Q000493:pharmacokinetics* / Q000633:toxicity; D058846:Antibodies, Monoclonal, Murine-Derived; D016503:Drug Delivery Systems / Q000379:methods*; D018796:Immunoconjugates / Q000737:chemistry / Q000627:therapeutic use*; D008187:Lutetium / Q000737:chemistry / Q000627:therapeutic use; D008251:Macaca; D008297:Male; D011868:Radioisotopes; D011874:Radiometry; D000069283:Rituximab
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018796:Immunoconjugates; D011868:Radioisotopes; D000069283:Rituximab; D008187:Lutetium