In this study, we investigated the ability of L-lysine to block renal uptake of 125I- or 99mTc- labeled Fv fragments. Anti-Tac disulfide- stabilized Fv fragment (dsFv) was derived from a murine monoclonal antibody that recognizes the α subunit of the interleukin-2 receptor (IL-2Rα). The 125I- or 99mTc-labeled dsFv was injected i.v. into non-tumor-bearing nude mice or into nude mice bearing SP2/Tac (IL-2Rα positive) and SP2/0 (IL-2Rα negative) tumor. We then evaluated the pharmacokinetics of L- [3H]lysine and the effect of L-lysine dose, timing of administration, and route of delivery on catabolism and biodistribution of i.v. dsFv. Peak renal uptake of i.v. or i.p. injected L-[3H]lysine occurred within 5 and 15 min, respectively. The kidney uptake of L-lysine exhibited a dose-response effect. When L-lysine was coinfused or injected shortly before dsFv, renal uptake of dsFv was blocked to <5% of the control, but longer intervals were less effective. 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 uptake 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 immediately before the injection of radiolabeled dsFv, is most effective in blocking the renal uptake of dsFv. This is consistent with the rapid uptake of L-[3H]lysine by the kidney and is further substantiated by the relative ineffectiveness of lysine injected immediately after the radiolabeled dsFv injection.
|Number of pages||8|
|Publication status||Published - 1996 Aug 15|
ASJC Scopus subject areas
- Cancer Research