Strategies to reduce renal radioactivity levels of antibody fragments

Antibody fragments such as Fab and single-chain Fv fragments possess many a dvantages over intact antibodies as vehicles to deliver radioactivity for d iagnostic and therapeutic applications. However, radiolabeled antibody frag ments exhibited high and persistent localization of the radioactivity in th e kidney, which compromises diagnostic accuracy and therapeutic effectivene ss, Recent studies indicated that the persistent localization of renal radi oactivity would be originated from the re-absorption of glomerularly-filter ed radiolabeled antibody fragments, followed by the retention of the radiom etabolites generated after degradation in the lysosomal compartment of the renal cells. Two major approaches have been performed to reduce the renal r adioactivity levels of antibody fragments. One is to block the reabsorption of radiolabeled antibody fragments themselves at the proximal tubular cell s from the luminal fluid by administration of basic amino acids such as L-l ysine. The other approach is to decrease the residence time of the radiomet abolites within the lysosomal compartments of the renal cells by introducin g a cleavable linkage between antibody fragments and radiometabolites of ra pid urinary excretion. Another approach to reduce renal radioactivity level s of antibody fragments may be to release radiolabeled compound of urinary excretion from glomerularly-filtered antibody fragments before they are rea bsorbed 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 f ragments are briefly reviewed.