These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Biological properties of biotin-chelate conjugates for pretargeted diagnosis and therapy with the avidin/biotin system.
    Author: Goodwin DA, Meares CF, Osen M.
    Journal: J Nucl Med; 1998 Oct; 39(10):1813-8. PubMed ID: 9776294.
    Abstract:
    UNLABELLED: Three-step pretargeting increases target-to-background ratios in radioimmunodetection and can potentially decrease harmful radiation to normal tissues in radioimmunotherapy. We studied four biotin-chelate conjugates (BCCs) for use in the avidin/biotin pretargeting system. METHODS: Pharmacokinetics and biodistribution were studied in normal BALB/c (IAk-negative), normal C3H (IAk-positive) and LS174T tumor-bearing BALB/c severe combined immunodeficient mice. Streptavidin alone and antibody-streptavidin conjugates [monoclonal antibody (MAb) 10-3.6 anti-IAk IgG2a] were used. Indium-111- or 88Y-BCCs were given alone intravenously; they were mixed with streptavidin or MAb-streptavidin conjugate and given intravenously; or streptavidin and MAb-streptavidin conjugate were pretargeted, and 2-3, 5 and 21 hr later, BCCs were injected intravenously. Samples were taken 2-3 hr after intravenous injection of labeled BCCs. RESULTS: Three of the four BCCs were rapidly excreted by the kidneys, with <2.5%/g in any organ or tumor at 2-3 hr. Gut excretion eliminated biotinyl-(S)-1-p-aminobenzylethylenediaminetetraacetic acid (EDTA) for use in pretargeting. Ninety percent of BCCs were bound to circulating pretargeted streptavidin at 1-6 hr, and approximately 15% were bound to pretargeted streptavidin at 24 hr. Kidney uptakes were: preformed streptavidin-BCC given intravenously, approximately 80%/g (24 hr); streptavidin pretargeted for 2-3 hr, approximately 60%/g; and streptavidin pretargeted for 5-21 hr, approximately 10%-20%/g. Kidney uptake was dose-dependent: 0.2, 0.67 and 1.0 nmol of streptavidin pretargeted for 21 hr showed increasing concentrations (24 hr). Uptake of monoclonal anti-IAk-streptavidin-BCC complex into spleen (70% +/- 10%/g; p < 0.05) and lymph nodes (10% +/- 3.5%/g; p < 0.01) was higher in IAk-positive C3H mice than it was in IAk-negative control BALB/c mice, and it was much higher than that in streptavidin controls. No significant target uptake was seen with anti-IAk MAb-streptavidin pretargeted for 3 or 20 hr. Kidney uptake approximately 20%/g, which was lower than that of streptavidin alone. CONCLUSION: Three biotinyl chelates bind the diagnostic and therapeutic radiometals 111In and 88Y (and, by analogy, 90Y) with the required in vivo stability and physiological properties for pretargeted diagnosis and therapy. Kidney uptake of streptavidin was decreased by conjugation to MAb. Failure of anti IAk MAb-streptavidin conjugate to bind BCC after pretargeting may be due to rapid internalization of MAb-streptavidin-IAk complex by the lymphocyte or to endogenous biotin. Either or both of these would make streptavidin unavailable to subsequent BCCs.
    [Abstract] [Full Text] [Related] [New Search]