A general, extracorporeal immunoadsorption method to increase the tumor-to-normal tissue ratio in radioimmunoimaging and radioimmunotherapy.
The aim of this study was to investigate a new extracorporeal immunoadsorption method to improve tumor-to-normal tissue ratios in radioimmunoimaging (RII) and radioimmunotherapy (RIT). We have developed and investigated a general method using biotinylated antibodies and an agarose-avidin column for extracorporeal immunoadsorption. The studies were made in an animal model and extracorporeal immunoadsorption (ECIA) was performed 24 or 48 hr after the injection of 125I-labeled biotinylated antibodies. In athymic rats, heterotransplanted with human malignant melanoma, 90%-95% of the circulating activity was removed with ECIA. The tumor-to-normal tissue ratios at 24 hr was increased 4 times (from 1.2 to 5.1) in the liver, 2.5 times (0.7 to 1.8) in the lung, 4 times (1 to 4) in the kidneys and 4 times (1.4 to 5) in the bone marrow. Whole body activity was reduced by 40%-50%. Tumor-to-organ ratios at 48 hr were increased 3.5 times (from 1.5 to 5.2) in the liver, 2 times (0.9 to 1.7) in the lung, 3 times (1.3 to 3.8) in the kidneys and 4 times (1.4 to 5.5) in the bone marrow. Whole body activity was reduced by 35% when ECIA was performed 48 hr after injection. This study proves that an important reduction in background activity, and thereby an improvement in the tumor-to-background ratio, can be achieved by using this generally applicable, biotin-avidin ECIA method. For RII, the improved ratio increases the possibilities of detecting tumors and metastases in blood-rich organs. For RIT, the procedure may lead to a decreased absorbed dose to bone marrow and other critical organs.
Norrgren
K
K
Department of Radiation Physics, University of Lund, Sweden.
Strand
S E
SE
Nilsson
R
R
Lindgren
L
L
Sjögren
H O
HO
D000818:Animals; D001360:Avidin; D001710:Biotin; D005260:Female; D008297:Male; D008546:Melanoma, Experimental / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D010956:Plasmapheresis; D016719:Radioimmunodetection / Q000379:methods; D016499:Radioimmunotherapy / Q000379:methods; D051381:Rats; D011923:Rats, Nude; D014018:Tissue Distribution
D001360:Avidin; D001710:Biotin