Protein radiohalogenation: observations on the design of N-succinimidyl ester acylation agents.

Journal Article (Journal Article)

In previous studies we have demonstrated that antibodies radioiodinated with N-succinimidyl 3-iodobenzoate (SIB) are less susceptible to loss of radioiodine in vivo than antibodies iodinated directly by electrophilic substitution on their tyrosine residues with Iodogen. Since the Bolton-Hunter reagent, N-succinimidyl 3-(4-hydroxy-3-iodophenyl)propionate, is identical with SIB except that it contains a hydroxyl group on the aromatic ring and a two-methylene spacer, a comparison of their coupling chemistry and in vivo behavior was performed to better understand the structural requirements for a useful iodinated acylation agent. Protein concentration and pH had a significant effect on the coupling efficiency of both SIB and the Bolton-Hunter reagent; however, protein-labeling yields with SIB were generally higher by a factor of 2. Paired-label biodistribution studies in mice demonstrated that thyroid uptake (a monitor of dehalogenation) of antibody labeled by the Bolton-Hunter method was twice that of antibody labeled with SIB but only 7% of that observed for antibody labeled with Iodogen. These results suggest that even minor differences in iodination site can profoundly alter the retention of label on a protein in vivo.

Full Text

Duke Authors

Cited Authors

  • Vaidyanathan, G; Zalutsky, MR

Published Date

  • July 1, 1990

Published In

Volume / Issue

  • 1 / 4

Start / End Page

  • 269 - 273

PubMed ID

  • 2096920

International Standard Serial Number (ISSN)

  • 1043-1802

Digital Object Identifier (DOI)

  • 10.1021/bc00004a007


  • eng

Conference Location

  • United States