Extracorporeal immunoadsorption compared to avidin chase: enhancement of tumor-to-normal tissue ratio for biotinylated rhenium-188-chimeric BR96.

Abstract

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. 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. 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. 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.