Biocompatibility of a novel avidin-agarose adsorbent for extracorporeal removal of redundant radiopharmaceutical from the blood.
The use of monoclonal antibodies (MAbs) in cytotoxic conjugates (radionuclides, toxins, or drugs) for targeting tumor cells is restricted due to toxicity in vital organs. Through improved tumor targeting, it is possible to administer larger amounts of such labeled MAbs, thus improving the ability to eradicate tumor cells without increased normal organ toxicity. Extracorporeal affinity adsorption treatment (ECAT) has therefore been developed using an avidin-agarose (AA) adsorbent with high binding affinity for the biotinylated radiolabeled MAb, rituximab. During ECAT, excess radioimmunoconjugates, not bound to the tumor cells, can be removed improving tumor targeting. The present study was performed to estimate the biocompatibility of the AA adsorber. Seven patients with B-cell lymphoma not responding to conventional treatment were studied. During the ECAT procedure, blood (B) components, plasma (P) complement fragments C3a, C5a, and P-bradykinin were analyzed, and other laboratory tests were carried out. Slight decreases in B-hemoglobin (8.3%), B-thrombocytes (11.4%), and P-albumin (14.3%) were observed, and could be explained by the dilution of the blood with normal saline and acid citrate dextrose. The AA adsorbent had no effect on the blood cells, immunological status or P-bradykinin level. The AA adsorber demonstrated good hemocompatibility and biocompatibility, without any side effects in the patients.
Kurkus
Jan
J
Department of Nephrology, Lund University Hospital, SE-221 85 Lund, Sweden. jan.kurkus@med.lu.se
Nilsson
Rune
R
Lindén
Ola
O
Schönström
Niki
N
Sandberg
Bengt E B
BE
Tennvall
Jan
J
D000327:Adsorption; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001360:Avidin / Q000097:blood / Q000737:chemistry / Q000627:therapeutic use*; D005112:Extracorporeal Circulation / Q000295:instrumentation*; D005260:Female; D006464:Hemoperfusion / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000532:radiotherapy*; D008297:Male; D008422:Materials Testing; D008875:Middle Aged; D016499:Radioimmunotherapy / Q000379:methods*; D011868:Radioisotopes / Q000737:chemistry / Q000627:therapeutic use; D016879:Salvage Therapy / Q000379:methods; D012685:Sepharose / Q000097:blood / Q000737:chemistry / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D011868:Radioisotopes; C066402:avidin-agarose; D001360:Avidin; D012685:Sepharose