Document Detail


Extracorporeal adsorption therapy: a method to improve targeted radiation delivered by radiometal-labeled monoclonal antibodies.
MedLine Citation:
PMID:  18454687     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: 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.
EXPERIMENTAL DESIGN: 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:
Eneida R Nemecek; Damian J Green; Darrell R Fisher; John M Pagel; Yukang Lin; Ajay K Gopal; Lawrence D Durack; Joseph G Rajendran; D Scott Wilbur; Rune Nilsson; Bengt Sandberg; Oliver W Press
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer biotherapy & radiopharmaceuticals     Volume:  23     ISSN:  1557-8852     ISO Abbreviation:  Cancer Biother. Radiopharm.     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-05-05     Completed Date:  2008-08-12     Revised Date:  2013-03-22    
Medline Journal Info:
Nlm Unique ID:  9605408     Medline TA:  Cancer Biother Radiopharm     Country:  United States    
Other Details:
Languages:  eng     Pagination:  181-91     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, Oregon Health & Science University, Portland, OR, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / chemistry,  immunology*,  pharmacokinetics*,  toxicity
Antibodies, Monoclonal, Murine-Derived
Drug Delivery Systems / methods*
Immunoconjugates / chemistry,  therapeutic use*
Lutetium / chemistry,  therapeutic use
Macaca
Male
Radioisotopes
Radiometry
Grant Support
ID/Acronym/Agency:
CA100394/CA/NCI NIH HHS; CA109663/CA/NCI NIH HHS; CA44991/CA/NCI NIH HHS; P01 CA044991/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antibodies, Monoclonal, Murine-Derived; 0/Immunoconjugates; 0/Radioisotopes; 0/rituximab; 7439-94-3/Lutetium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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