RENAL ACCUMULATION OF STREPTAVIDIN - POTENTIAL USE FOR TARGETED THERAPY TO THE KIDNEY

Streptavidin exhibits a remarkable accumulation in the kidney. Biodistribution studies with radio-iodinated streptavidin showed that 70 to 80% of the injected dose per gram tissue (%/g) were retained in kidneys of Balb/C mice for three to four days compared to less than 5 %/g levels in other tissues. This observation means that 15 to 20% of the injected dose is accumulated in the kidney, an organ that constitutes less than 1% of total body weight. Similar results of percent radioactivity per total kidney were obtained in other mouse strains as well as in rats and rabbits. Avidin, or the post-secretory form of streptavidin which is of a higher molecular weight, do not show any preferential affinity to the kidney. The kidney-accumulated streptavidin was mostly confined to the cortex, concentrated in the proximal tubular cells. Accumulation of streptavidin in the kidney was independent of biotin, since addition of biotin to radio-iodinated streptavidin prior to injection did not affect its kidney uptake. Therefore, streptavidin, which aquires its kidney accumulation property following truncation of the native form, may be utilized for renal specific delivery of chemotherapeutic agents, radioactive isotopes and other effector molecules. Such ligands can be linked to streptavidin via conventional coupling methods or following their biotinylation. Preliminary experiments showed that streptavidin can target to the kidney biotinylated ligands or high doses of chemically linked radionuclides.