Extracorporeal adsorption therapy: a method to improve targeted radiation delivered by radiometal-labeled monoclonal antibodies.
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.
Nemecek
Eneida R
ER
Department of Pediatrics, Oregon Health & Science University, Portland, OR, USA.
Green
Damian J
DJ
Fisher
Darrell R
DR
Pagel
John M
JM
Lin
Yukang
Y
Gopal
Ajay K
AK
Durack
Lawrence D
LD
Rajendran
Joseph G
JG
Wilbur
D Scott
DS
Nilsson
Rune
R
Sandberg
Bengt
B
Press
Oliver W
OW
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
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018796:Immunoconjugates; D011868:Radioisotopes; D000069283:Rituximab; D008187:Lutetium