Strategies to reduce renal radioactivity levels of antibody fragments.

Antibody fragments such as Fab and single-chain Fv fragments possess many advantages over intact antibodies as vehicles to deliver radioactivity for diagnostic and therapeutic applications. However, radiolabled antibody fragments exhibited high and persistent localization of the radioactivity in the kidney, which compromises diagnostic accuracy and therapeutic effectiveness. Recent studies indicated that the persistent localization of renal radioactivity would be originated from the re-absorption of glomerularly-filtered radiolabeled antibody fragments, followed by the retention of the radiometabolites generated after degradation in the lysosomal compartment of the renal cells. Two major approaches have been performed to reduce the renal radioactivity levels of antibody fragments. One is to block the reabsorption of radiolabeled antibody fragments themselves at the proximal tubular cells from the luminal fluid by administration of basic amino acids such as L-lysine. The other approach is to decrease the residence time of the radiometabolites within the lysosomal compartments of the renal cells by introducing a cleavable linkage between antibody fragments and radiometabolites of rapid urinary excretion. Another approach to reduce renal radioactivity levels of antibody fragments may be to release radiolabeled compound of urinary excretion from glomerularly-filtered antibody fragments before they are reabsorbed into the renal cells by the action of brush border enzymes present on the lumen of the renal proximal cells. In this paper, recent studies of the three approaches to reduce the renal radioactivity levels of antibody fragments are briefly reviewed.