Biological Properties of Biotin--Chelate Conjugates for Pretargeted Diagnosis and Therapy with the Avidin/Biotin System

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. 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. Three of the four BCCs were rapidly excreted by the kidneys, with