TY - JOUR
T1 - Extracorporeal adsorption therapy
T2 - A method to improve targeted radiation delivered by radiometal-labeled monoclonal antibodies
AU - Nemecek, Eneida R.
AU - Green, Damian J.
AU - Fisher, Darrell R.
AU - Pagel, John M.
AU - Lin, Yukang
AU - Gopal, Ajay K.
AU - Durack, Lawrence D.
AU - Rajendran, Joseph G.
AU - Wilbur, D. Scott
AU - Nilsson, Rune
AU - Sandberg, Bengt
AU - Press, Oliver W.
PY - 2008/4/1
Y1 - 2008/4/1
N2 - 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.
AB - 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.
KW - Lymphoma
KW - Monoclonal antibodies
KW - Primates
KW - Radioimmunotherapy
KW - Rituximab
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UR - http://www.scopus.com/inward/citedby.url?scp=43049086688&partnerID=8YFLogxK
U2 - 10.1089/cbr.2007.0433
DO - 10.1089/cbr.2007.0433
M3 - Article
C2 - 18454687
AN - SCOPUS:43049086688
SN - 1084-9785
VL - 23
SP - 181
EP - 191
JO - Cancer Biotherapy and Radiopharmaceuticals
JF - Cancer Biotherapy and Radiopharmaceuticals
IS - 2
ER -