IMPROVED TUMOR-LOCALIZATION WITH (STREPT)AVIDIN AND LABELED BIOTIN AS A SUBSTITUTE FOR ANTIBODY

Because of its short physical half life, the use of anti-tumor antibodies radiolabeled with Tc-99m has necessitated early (i.e. 2-6h post-administration) imaging. It is possible that at these early times localization of antibodies in certain tumors may be largely due to non-specific processes. If so, other proteins or agents may be preferred for early imaging of solid tumors. We have investigated tumor localization with labeled biotin administered subsequent to unlabeled and unconjugated streptavidin. Nude mice bearing anti-CEA tumors (LS174T) received 10 mug of In-111-labeled anti-CEA antibody (C110) or In-111-labeled streptavidin with sacrifice 5h later. In an examination of pretargeting, other animals received 50 mug of unlabeled streptavidin followed 3 h later with 1 mug of In-111-labeled biotin (EB1) and sacrifice 2h later. The biodistribution of labeled streptavidin was similar to that of labeled specific antibody except for lower blood and higher kidney levels. Tumor levels were also lower with labeled streptavidin but, because of still lower levels in liver and blood, the tumor/normal tissue ratios were improved. When unlabeled streptavidin was administered and followed by labeled biotin (pretargeting), tumor levels were further reduced modestly; however, normal tissue levels were greatly reduced such that the tumor/blood and tumor/liver ratios were 10.6 and 2.2 vs 1.5 and 0.5 for the specific antibody. Improvements were seen in all tissues sampled with the exception of kidney and muscle. A further control of labeled biotin alone (without the preinjection of streptavidin) showed minimal accumulations in all tissues with the exception of kidneys. In conclusion, the accumulation of (strept)avidin by passive diffusion in tumor may be comparable, at early times, to the accumulation of specific antibody. By combining the administration of unlabeled (strept)avidin with labeled biotin, tumor targeting may potentially be improved.