Improving radioimmonotargeting of tumors. Variation in the amount of L6 MAb administered, combined with an immunoadsorption system (ECIA).
Extracorporeal immunoadsorption (ECIA) is a new method for the selective removal of circulating radiolabeled monoclonal antibodies (MAb) from plasma to increase the uptake in tumor versus normal tissues (T/N-ratio). To ascertain whether the amount of MAb affects T/N ratios immediately and 24 h after ECIA, we used a rat model with two tumor sites--one intramuscular (im) and one below the subrenal capsule (SR). Extracorporeal immunoadsorption was done with an avidin-agarose column after injection of 125I-labeled biotinylated L6 MAb. The animals received 10, 50 or 250 micrograms of L6 only (controls), or followed by ECIA. The efficacy of the procedure in removing plasma activity was 80-95%. For both tumor sites, the highest T/N-ratios were obtained with 10 micrograms L6. All T/N-ratios significantly improved for SR tumors by a factor ranging from 3.2 (lung) to 12.6 (bone marrow). The T/N-ratios were still elevated 24 h after ECIA. Injection of larger amounts of MAb, probably causing a higher degree of tumor saturation, will not necessarily improve the T/N ratio after ECIA.
Garkavij
M
M
Department of Oncology, Lund University, Sweden.
Tennvall
J
J
Strand
S E
SE
Norrgren
K
K
Nilsson
R
R
Lindgren
L
L
Sjögren
H O
HO
D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000378:metabolism / Q000532:radiotherapy*; D000327:Adsorption; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D000954:Antigens, Surface / Q000276:immunology* / Q000378:metabolism; D001822:Body Burden; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000532:radiotherapy*; D008297:Male; D009363:Neoplasm Proteins / Q000276:immunology* / Q000378:metabolism; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy; D016719:Radioimmunodetection / Q000379:methods; D016499:Radioimmunotherapy / Q000379:methods*; D011868:Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use; D051381:Rats; D011923:Rats, Nude; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D007457:Iodine Radioisotopes; D009363:Neoplasm Proteins; D011868:Radioisotopes; C074075:TM4SF1 protein, human