158
Bioconjugate Chem. 2008, 19, 158–170
Streptavidin in Antibody Pretargeting. 5. Chemical Modification of Recombinant Streptavidin for Labeling with the r-Particle-Emitting Radionuclides 213Bi and 211At D. Scott Wilbur,*,† Donald K. Hamlin,† Ming-Kuan Chyan,† and Martin W. Brechbiel‡ Department of Radiation Oncology, University of Washington, Seattle, Washington, and National Cancer Institute, National Institutes of Health, Bethesda, Maryland. Received June 30, 2007; Revised Manuscript Received September 29, 2007
We are investigating the use of recombinant streptavidin (rSAv) as a carrier molecule for the short-lived R-particleemitting radionuclides 213Bi (t1/2 ) 45.6 min) and 211At (t1/2 ) 7.21 h) in cancer therapy. To utilize rSAv as a carrier, it must be modified in a manner that permits rapid chelation or bonding with these short-lived radionuclides and also modified in a manner that diminishes its natural propensity for localization in the kidney. Modification for labeling with 213Bi was accomplished by conjugation of rSAv with the DTPA derivative p-isothiocyanatobenzyl-CHX-A′′ (CHX-A′′), 3a. Modification for direct labeling with 211At was accomplished by conjugation of rSAv with an isothiocyanatophenyl derivative of a nido-carborane (nCB), 3b, or an isothiocyanatophenyl-dPEG/ decaborate(2-) derivative, 3c. After conjugation of the chelating or bonding moiety, rSAv was further modified by reaction with an excess (50–100 equivalents) of succinic anhydride. Succinylation of the lysine amines has previously been shown to greatly diminish kidney localization. rSAv modified by conjugation with 3a and succinylated rapidly radiolabeled with 213Bi (
