Extracorporeal immunoadsorption compared to avidin chase: enhancement of tumor-to-normal tissue ratio for biotinylated rhenium-188-chimeric BR96.
Based on the biodistribution and kinetics of biotinylated 188Re-chimeric BR96 (chiBR96), the enhancement of the tumor-to-normal tissue (T/N) radioactivity ratio using extracorporeal immunoadsorption (ECIA) was evaluated and compared with that of avidin "chase" in colon carcinoma-isografted Brown Norwegian rats.


METHODS
Extracorporeal immunoadsorption (ECIA) was performed 6 or 12 hr after intravenous administration of biotinylated 188Re-chiBR96. Radioactivity redistribution was investigated just after ECIA [8 or 14 hr postinjection of the antibody] and 40 or 34 hr after ECIA performance (48 hr postinjection). Avidin was administered intraperitoneally at 6 hr postinjection. Tumor radioactivity uptake and T/N activity ratios of biotinylated 188Re-chiBR96 were compared using ECIA and avidin chase and were also compared with controls.


RESULTS
Both ECIA and avidin chase can rapidly increase the radioactivity tumor-to-blood ratio without significantly interfering with the tumor uptake. ECIA at 8 hr postinjection increased the T/N ratios in blood-rich tissues, such as liver and bone marrow, from 6 and 8 to 10 and 18, respectively. Corresponding T/N ratios at 14 hr increased from 9 and 10 to 24 and 36. In contrast, when avidin chase was used, there were no T/N improvements, except in blood. Moreover, avidin chase caused a significant accumulation of radioactivity in the liver.


CONCLUSIONS
The ECIA approach, with direct removal of unbound circulating biotinylated 188Re-chiBR96, thus can rapidly improve and maintain T/N ratios without overloading the liver with radioactivity, in contrast to avidin chase.
Chen
J Q
JQ
Department of Radiation Physics, Lund University, Sweden.
Strand
S E
SE
Tennvall
J
J
Lindgren
L
L
Hindorf
C
C
Sjögren
H O
HO
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use; D001360:Avidin / Q000494:pharmacology; D001710:Biotin / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D006801:Humans; D007163:Immunosorbent Techniques; D008297:Male; D051379:Mice; D016499:Radioimmunotherapy / Q000379:methods*; D011868:Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011877:Radionuclide Imaging; D051381:Rats; D011914:Rats, Inbred BN; D012211:Rhenium / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D011868:Radioisotopes; D001360:Avidin; D001710:Biotin; D012211:Rhenium