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N-succinimidyl 3-[(131)I]iodo-4-phosphonomethylbenzoate ([(131)I]SIPMB), a negatively charged substituent-bearing acylation agent for the radioiodination of peptides and mAbs.

Publication ,  Journal Article
Shankar, S; Vaidyanathan, G; Affleck, D; Welsh, PC; Zalutsky, MR
Published in: Bioconjug Chem
2003

An important criterion in design of acylation agents for the radioiodination of internalizing monoclonal antibodies (mAbs) is to maximize the retention of radioiodine in the tumor following mAb intracellular processing. We have previously shown that labeling methods that generate positively charged catabolites have enhanced tumor retention. Herein we have extended this strategy to investigate the potential utility of labeling internalizing mAbs with an acylation agent that yielded labeled catabolites that would be negatively charged at lysosomal pH. The negatively charged acylation agent, N-succinimidyl 3-[(131)I]iodo-4-phosphonomethylbenzoate ([(131)I]SIPMB), was prepared from its tin precursor, N-succinimidyl 4-di-tert-butylphosphonomethyl-3-trimethylstannylbenzoate (tBu-SPMTB), in 40% radiochemical yield. The free acid, 3-[(131)I]iodo-4-phosphonomethylbenzoic acid ([(131)I]IPMBA), was also prepared from the corresponding precursor, 4-di-tert-butylphosphonomethyl-3-trimethylstannylbenzoic acid (tBu-PMTBA), in 80% radiochemical yield. The rapidly internalizing mAb L8A4 was conjugated to [(131)I]SIPMB in 25-40% yield with preservation of its immunoreactivity. Internalization and processing in the U87DeltaEGFR glioma cell line was studied in a paired label format with L8A4 labeled with (125)I using the Iodogen method. Retention of initially bound radioactivity in these cells at 24 h from [(131)I]SIPMB-labeled mAb was approximately 6-fold higher than that for directly labeled mAb. Catabolite analysis demonstrated that this difference reflected an order of magnitude higher retention of low molecular weight species in these cells. The [(131)I]SIPMB-L8A4 conjugate was intact over the first 2 h; thereafter, lysine-[(131)I]SIPMB was the predominant catabolite. In contrast, L8A4 labeled using Iodogen rapidly gave rise to mono-[(125)I]iodotyrosine within 2 h, which then cleared rapidly from the cells. These results suggest that SIPMB could be a potent candidate for labeling internalizing mAbs and warrant further study.

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Published In

Bioconjug Chem

DOI

ISSN

1043-1802

Publication Date

2003

Volume

14

Issue

2

Start / End Page

331 / 341

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Succinimides
  • Peptides
  • Organic Chemistry
  • Isotope Labeling
  • Iodine Radioisotopes
  • Indicators and Reagents
  • Chromatography, High Pressure Liquid
  • Benzoates
  • Antibodies, Monoclonal
 

Citation

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Shankar, S., Vaidyanathan, G., Affleck, D., Welsh, P. C., & Zalutsky, M. R. (2003). N-succinimidyl 3-[(131)I]iodo-4-phosphonomethylbenzoate ([(131)I]SIPMB), a negatively charged substituent-bearing acylation agent for the radioiodination of peptides and mAbs. Bioconjug Chem, 14(2), 331–341. https://doi.org/10.1021/bc025636p
Shankar, Sriram, Ganesan Vaidyanathan, Donna Affleck, Phillip C. Welsh, and Michael R. Zalutsky. “N-succinimidyl 3-[(131)I]iodo-4-phosphonomethylbenzoate ([(131)I]SIPMB), a negatively charged substituent-bearing acylation agent for the radioiodination of peptides and mAbs.Bioconjug Chem 14, no. 2 (2003): 331–41. https://doi.org/10.1021/bc025636p.
Journal cover image

Published In

Bioconjug Chem

DOI

ISSN

1043-1802

Publication Date

2003

Volume

14

Issue

2

Start / End Page

331 / 341

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Succinimides
  • Peptides
  • Organic Chemistry
  • Isotope Labeling
  • Iodine Radioisotopes
  • Indicators and Reagents
  • Chromatography, High Pressure Liquid
  • Benzoates
  • Antibodies, Monoclonal