L-LYSINE EFFECTIVELY BLOCKS RENAL UPTAKE OF I-125-LABELED OR TC-99M-LABELED ANTI-TAC DISULFIDE-STABILIZED FV FRAGMENT

In this study, me investigated the ability of L-lysine to block renal uptake of I-125-, Tc-99m- labeled Fv fragments. Anti-Tac disulfide-sta bilized Fv fragment (dsFv) was derived from a murine monoclonal antibo dy that recognizes the alpha subunit of the interleukin-2 receptor (IL -2R alpha). The I-125- or Tc-99m-labeled dsFv was injected i.v. into n on-tumor-hearing nude mice or into nude mice hearing SP2/Tac (IL-2R al pha positive) and SP2/0 (IL-2R alpha negative) tumor. We then evaluate d the pharmacokinetics of L-[H-3]lysine and the effect of L-lysine dos e, timing of administration, and route of delivery on catabolism and b iodistribution of i.v. dsFv. Peak renal uptake of i.v. or i.p. injecte d L-[H-3]lysine occurred within 5 and 15 min, respectively. The kidney uptake of L-lysine exhibited a dose-response effect. When L-lysine wa s coinfused or injected shortly before dsFv, renal uptake of dsFv was blocked to <5% of the control, but longer intervals were less effectiv e. Aminosyn II and Travasol 10% (parenteral amino acid solutions) also blocked renal uptake of radiolabeled dsFv. Administration of L-lysine did not alter the blood kinetics and slightly increased the tumor upt ake of dsFv, but it did prevent catabolism in the kidney and resulted in lower amounts of catabolites In the serum and urine. In conclusion, we have shown that a blocking dose of lysine, injected with or immedi ately before the injection of radiolabeled dsFv, is most effective in blocking the renal uptake of dsFv. This is consistent with the rapid u ptake of L-[H-3]lysine by the kidney and is further substantiated by t he relative ineffectiveness of lysine injected immediately after the r adiolabeled dsFv injection.