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Nepsilon-(3-[*I]Iodobenzoyl)-Lys5-Nalpha-maleimido-Gly1-GEEEK ([*I]IB-Mal-D-GEEEK): a radioiodinated prosthetic group containing negatively charged D-glutamates for labeling internalizing monoclonal antibodies.

Publication ,  Journal Article
Vaidyanathan, G; Alston, KL; Bigner, DD; Zalutsky, MR
Published in: Bioconjug Chem
2006

Novel methods are needed for the radiohalogenation of cell-internalizing proteins and peptides because rapid loss of label occurs after lysosomal processing when these molecules are labeled using conventional radioiodination methodologies. We have developed a radiolabeled prosthetic group that contains multiple negatively charged D-amino acids to facilitate trapping of the radioactivity in the cell after proteolysis of the labeled protein. N(epsilon)-(3-[(125)I]iodobenzoyl)-Lys(5)-N(alpha)-maleimido-Gly(1)-GEEEK ([(125)I]IB-Mal-D-GEEEK) was synthesized via iododestannylation in 90.3 +/- 3.9% radiochemical yields. This radioiodinated agent was conjugated to iminothiolane-treated L8A4, an anti-epidermal growth factor receptor variant III (EGFRvIII) specific monoclonal antibody (mAb) in 54.3 +/- 17.7% conjugation yields. In vitro assays with the EGFRvIII-expressing U87MGDeltaEGFR glioma cell line demonstrated that the internalized radioactivity for the [(125)I]IB-Mal-D-GEEEK-L8A4 conjugate increased from 14.1% at 1 h to 44.7% at 24 h and was about 15-fold higher than that of directly radioiodinated L8A4 at 24 h. A commensurately increased tumor uptake in vivo in athymic mice bearing subcutaneous U87MGDeltaEGFR xenografts (52.6 +/- 14.3% injected dose per gram versus 17.4 +/- 3.5% ID/g at 72 h) also was observed. These results suggest that [(125)I]IB-Mal-d-GEEEK is a promising reagent for the radioiodination of internalizing mAbs.

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Published In

Bioconjug Chem

DOI

ISSN

1043-1802

Publication Date

2006

Volume

17

Issue

4

Start / End Page

1085 / 1092

Location

United States

Related Subject Headings

  • Tissue Distribution
  • Organic Chemistry
  • Oligopeptides
  • Mice
  • Iodobenzenes
  • Iodine Radioisotopes
  • Glutamic Acid
  • Glioma
  • Cell Line, Tumor
  • Brain Neoplasms
 

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Vaidyanathan, G., Alston, K. L., Bigner, D. D., & Zalutsky, M. R. (2006). Nepsilon-(3-[*I]Iodobenzoyl)-Lys5-Nalpha-maleimido-Gly1-GEEEK ([*I]IB-Mal-D-GEEEK): a radioiodinated prosthetic group containing negatively charged D-glutamates for labeling internalizing monoclonal antibodies. Bioconjug Chem, 17(4), 1085–1092. https://doi.org/10.1021/bc0600766
Vaidyanathan, Ganesan, Kevin L. Alston, Darrel D. Bigner, and Michael R. Zalutsky. “Nepsilon-(3-[*I]Iodobenzoyl)-Lys5-Nalpha-maleimido-Gly1-GEEEK ([*I]IB-Mal-D-GEEEK): a radioiodinated prosthetic group containing negatively charged D-glutamates for labeling internalizing monoclonal antibodies.Bioconjug Chem 17, no. 4 (2006): 1085–92. https://doi.org/10.1021/bc0600766.
Journal cover image

Published In

Bioconjug Chem

DOI

ISSN

1043-1802

Publication Date

2006

Volume

17

Issue

4

Start / End Page

1085 / 1092

Location

United States

Related Subject Headings

  • Tissue Distribution
  • Organic Chemistry
  • Oligopeptides
  • Mice
  • Iodobenzenes
  • Iodine Radioisotopes
  • Glutamic Acid
  • Glioma
  • Cell Line, Tumor
  • Brain Neoplasms