Immunotargeting of streptavidin to the pulmonary endothelium

V. R. Muzykantov, Elena Nikolaevna Atochina, V. Gavriljuk, S. M. Danilov, A. B. Fisher

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

We have observed previously that monoclonal antibody to angiotensin- converting enzyme (Mab 9B9) accumulates selectively in the lung after intravenous injection. The objective of the present work is the development of a universal system for targeting of drug or radiolabel to the lung, using biotinylated Mab 9B9 and streptavidin. Methods: Mab 9B9 was biotinylated with biotin succinimide ester (b-Mab 9B9), while streptavidin (SA) was radiolabeled with 125I. Interaction between b-Mab 9B9 and SA has been estimated in solid-phase radioassay. Radiolabeled SA was conjugated with b- Mab 9B9 or with b-IgG and injected intravenously in rats or perfused in isolated rat lungs. Results: Radiolabeled b-Mab 9B9 biotinylated at biotin- to-antibody molar ratio 10 (b-Mab 9B9) retains its ability to accumulate in rat lungs after intravenous injection. Radiolabeled SA conjugated with b-Mab 9B9 accumulates in the lung tissue in perfused isolated rat lungs. About 20% of injected SA accumulates in the rat lung 1 hr after intravenous injection (localization ratio is 20, immunospecificity of the conjugate pulmonary uptake is 70). As compared with conjugate injection, stepwise intravenous injection of b-Mab 9B9 and radiolabeled SA leads to a marked reduction of SA pulmonary uptake. Maximal pulmonary uptake of Mab 9B9 has been observed 2-3 hr after intravenous injection, while 24 hr later, radioactivity in the lung was markedly reduced. In contrast to radiolabeled Mab 9B9 alone, radiolabeled SA conjugated with b-Mab 9B9 was retained in the lung for at least 48 hr. In concert with effective blood clearance of the conjugate, its prolonged lung retention leads to a marked increase in its lung-to-blood ratio: 80 for SA- b-Mab 9B9 versus 15-20 for Mab 9B9. Conclusion: Conjugation of Mab 9B9 with streptavidin enhances selective pulmonary uptake of the preparation, providing a background for intrapulmonary immunotargeting of various biotinylated agents.

Original languageEnglish
Pages (from-to)1358-1365
Number of pages8
JournalJournal of Nuclear Medicine
Volume35
Issue number8
Publication statusPublished - 1994
Externally publishedYes

    Fingerprint

Keywords

  • angiotensin-converting enzyme
  • biotinylated antibody
  • endothelium
  • lung
  • streptavidin

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

Cite this

Muzykantov, V. R., Atochina, E. N., Gavriljuk, V., Danilov, S. M., & Fisher, A. B. (1994). Immunotargeting of streptavidin to the pulmonary endothelium. Journal of Nuclear Medicine, 35(8), 1358-1365.