L-lysine effectively blocks renal uptake of 125I- or 99mTc- labeled anti-Tac disulfide-stabilized Fv fragment

Hisataka Kobayashi, Tae M. Yoo, In S. Kim, Meyoung-Kon Kim, Nhat Le, Keith O. Webber, Ira Pastan, Chang H. Paik, William C. Eckelman, Jorge A. Carrasquillo

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Abstract

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.

Original languageEnglish
Pages (from-to)3788-3795
Number of pages8
JournalCancer Research
Volume56
Issue number16
Publication statusPublished - 1996 Aug 15
Externally publishedYes

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Immunoglobulin Variable Region
Disulfides
Lysine
Kidney
Interleukin-2 Receptors
Murine-Derived Monoclonal Antibodies
Nude Mice
Injections
Neoplasms
Pharmacokinetics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Kobayashi, H., Yoo, T. M., Kim, I. S., Kim, M-K., Le, N., Webber, K. O., ... Carrasquillo, J. A. (1996). L-lysine effectively blocks renal uptake of 125I- or 99mTc- labeled anti-Tac disulfide-stabilized Fv fragment. Cancer Research, 56(16), 3788-3795.

L-lysine effectively blocks renal uptake of 125I- or 99mTc- labeled anti-Tac disulfide-stabilized Fv fragment. / Kobayashi, Hisataka; Yoo, Tae M.; Kim, In S.; Kim, Meyoung-Kon; Le, Nhat; Webber, Keith O.; Pastan, Ira; Paik, Chang H.; Eckelman, William C.; Carrasquillo, Jorge A.

In: Cancer Research, Vol. 56, No. 16, 15.08.1996, p. 3788-3795.

Research output: Contribution to journalArticle

Kobayashi, H, Yoo, TM, Kim, IS, Kim, M-K, Le, N, Webber, KO, Pastan, I, Paik, CH, Eckelman, WC & Carrasquillo, JA 1996, 'L-lysine effectively blocks renal uptake of 125I- or 99mTc- labeled anti-Tac disulfide-stabilized Fv fragment', Cancer Research, vol. 56, no. 16, pp. 3788-3795.
Kobayashi, Hisataka ; Yoo, Tae M. ; Kim, In S. ; Kim, Meyoung-Kon ; Le, Nhat ; Webber, Keith O. ; Pastan, Ira ; Paik, Chang H. ; Eckelman, William C. ; Carrasquillo, Jorge A. / L-lysine effectively blocks renal uptake of 125I- or 99mTc- labeled anti-Tac disulfide-stabilized Fv fragment. In: Cancer Research. 1996 ; Vol. 56, No. 16. pp. 3788-3795.
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abstract = "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.",
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AU - Kim, In S.

AU - Kim, Meyoung-Kon

AU - Le, Nhat

AU - Webber, Keith O.

AU - Pastan, Ira

AU - Paik, Chang H.

AU - Eckelman, William C.

AU - Carrasquillo, Jorge A.

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