Extracorporeal adsorption therapy

A method to improve targeted radiation delivered by radiometal-labeled monoclonal antibodies

Eneida 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

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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 111In- or 177Lu-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 111In- or 177Lu-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.

Original languageEnglish (US)
Pages (from-to)181-191
Number of pages11
JournalCancer Biotherapy and Radiopharmaceuticals
Volume23
Issue number2
DOIs
StatePublished - Apr 1 2008

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Adsorption
Monoclonal Antibodies
Radiation
Immunoconjugates
Lymph Nodes
Macaca
Therapeutics
Kidney
Anti-Idiotypic Antibodies
Spleen
Bone Marrow
Injections
Gamma Cameras
Blood Volume
Non-Hodgkin's Lymphoma
B-Lymphocytes
Research Design
Lung
Antibodies
Liver

Keywords

  • Lymphoma
  • Monoclonal antibodies
  • Primates
  • Radioimmunotherapy
  • Rituximab

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Oncology

Cite this

Extracorporeal adsorption therapy : A method to improve targeted radiation delivered by radiometal-labeled monoclonal antibodies. / Nemecek, Eneida; Green, Damian J.; Fisher, Darrell R.; Pagel, John M.; Lin, Yukang; Gopal, Ajay K.; Durack, Lawrence D.; Rajendran, Joseph G.; Wilbur, D. Scott; Nilsson, Rune; Sandberg, Bengt; Press, Oliver W.

In: Cancer Biotherapy and Radiopharmaceuticals, Vol. 23, No. 2, 01.04.2008, p. 181-191.

Research output: Contribution to journalArticle

Nemecek, E, Green, DJ, Fisher, DR, Pagel, JM, Lin, Y, Gopal, AK, Durack, LD, Rajendran, JG, Wilbur, DS, Nilsson, R, Sandberg, B & Press, OW 2008, 'Extracorporeal adsorption therapy: A method to improve targeted radiation delivered by radiometal-labeled monoclonal antibodies', Cancer Biotherapy and Radiopharmaceuticals, vol. 23, no. 2, pp. 181-191. https://doi.org/10.1089/cbr.2007.0433
Nemecek, Eneida ; Green, Damian J. ; Fisher, Darrell R. ; Pagel, John M. ; Lin, Yukang ; Gopal, Ajay K. ; Durack, Lawrence D. ; Rajendran, Joseph G. ; Wilbur, D. Scott ; Nilsson, Rune ; Sandberg, Bengt ; Press, Oliver W. / Extracorporeal adsorption therapy : A method to improve targeted radiation delivered by radiometal-labeled monoclonal antibodies. In: Cancer Biotherapy and Radiopharmaceuticals. 2008 ; Vol. 23, No. 2. pp. 181-191.
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