Skip to main content
Journal cover image

N-Succinimidyl guanidinomethyl iodobenzoate protein radiohalogenation agents: influence of isomeric substitution on radiolabeling and target cell residualization.

Publication ,  Journal Article
Choi, J; Vaidyanathan, G; Koumarianou, E; McDougald, D; Pruszynski, M; Osada, T; Lahoutte, T; Lyerly, HK; Zalutsky, MR
Published in: Nucl Med Biol
2014

INTRODUCTION: N-succinimidyl 4-guanidinomethyl-3-[(*)I]iodobenzoate ([(*)I]SGMIB) has shown promise for the radioiodination of monoclonal antibodies (mAbs) and other proteins that undergo extensive internalization after receptor binding, enhancing tumor targeting compared to direct electrophilic radioiodination. However, radiochemical yields for [(131)I]SGMIB synthesis are low, which we hypothesize is due to steric hindrance from the Boc-protected guanidinomethyl group ortho to the tin moiety. To overcome this, we developed the isomeric compound, N-succinimidyl 3-guanidinomethyl-5-[(131)I]iodobenzoate (iso-[(131)I]SGMIB) wherein this bulky group was moved from ortho to meta position. METHODS: Boc2-iso-SGMIB standard and its tin precursor, N-succinimidyl 3-((1,2-bis(tert-butoxycarbonyl)guanidino)methyl)-5-(trimethylstannyl)benzoate (Boc2-iso-SGMTB), were synthesized using two disparate routes, and iso-[*I]SGMIB synthesized from the tin precursor. Two HER2-targeted vectors - trastuzumab (Tras) and a nanobody 5F7 (Nb) - were labeled using iso-[(*)I]SGMIB and [(*)I]SGMIB. Paired-label internalization assays in vitro with both proteins, and biodistribution in vivo with trastuzumab, labeled using the two isomeric prosthetic agents were performed. RESULTS: When the reactions were performed under identical conditions, radioiodination yields for the synthesis of Boc2-iso-[(131)I]SGMIB were significantly higher than those for Boc2-[(131)I]SGMIB (70.7±2.0% vs 56.5±5.5%). With both Nb and trastuzumab, conjugation efficiency also was higher with iso-[(131)I]SGMIB than with [(131)I]SGMIB (Nb, 33.1±7.1% vs 28.9±13.0%; Tras, 45.1±4.5% vs 34.8±10.3%); however, the differences were not statistically significant. Internalization assays performed on BT474 cells with 5F7 Nb indicated similar residualizing capacity over 6h; however, at 24h, radioactivity retained intracellularly for iso-[(131)I]SGMIB-Nb was lower than for [(125)I]SGMIB-Nb (46.4±1.3% vs 56.5±2.5%); similar results were obtained using Tras. Likewise, a paired-label biodistribution of Tras labeled using iso-[(125)I]SGMIB and [(131)I]SGMIB indicated an up to 22% tumor uptake advantage at later time points for [(131)I]SGMIB-Tras. CONCLUSION: Given the higher labeling efficiency obtained with iso-SGMIB, this residualizing agent might be of value for use with shorter half-life radiohalogens.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Nucl Med Biol

DOI

EISSN

1872-9614

Publication Date

2014

Volume

41

Issue

10

Start / End Page

802 / 812

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Tissue Distribution
  • Stereoisomerism
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Radiopharmaceuticals
  • Radionuclide Imaging
  • Nuclear Medicine & Medical Imaging
  • Mice
  • Isotope Labeling
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Choi, J., Vaidyanathan, G., Koumarianou, E., McDougald, D., Pruszynski, M., Osada, T., … Zalutsky, M. R. (2014). N-Succinimidyl guanidinomethyl iodobenzoate protein radiohalogenation agents: influence of isomeric substitution on radiolabeling and target cell residualization. Nucl Med Biol, 41(10), 802–812. https://doi.org/10.1016/j.nucmedbio.2014.07.005
Choi, Jaeyeon, Ganesan Vaidyanathan, Eftychia Koumarianou, Darryl McDougald, Marek Pruszynski, Takuya Osada, Tony Lahoutte, H Kim Lyerly, and Michael R. Zalutsky. “N-Succinimidyl guanidinomethyl iodobenzoate protein radiohalogenation agents: influence of isomeric substitution on radiolabeling and target cell residualization.Nucl Med Biol 41, no. 10 (2014): 802–12. https://doi.org/10.1016/j.nucmedbio.2014.07.005.
Choi J, Vaidyanathan G, Koumarianou E, McDougald D, Pruszynski M, Osada T, et al. N-Succinimidyl guanidinomethyl iodobenzoate protein radiohalogenation agents: influence of isomeric substitution on radiolabeling and target cell residualization. Nucl Med Biol. 2014;41(10):802–12.
Choi, Jaeyeon, et al. “N-Succinimidyl guanidinomethyl iodobenzoate protein radiohalogenation agents: influence of isomeric substitution on radiolabeling and target cell residualization.Nucl Med Biol, vol. 41, no. 10, 2014, pp. 802–12. Pubmed, doi:10.1016/j.nucmedbio.2014.07.005.
Choi J, Vaidyanathan G, Koumarianou E, McDougald D, Pruszynski M, Osada T, Lahoutte T, Lyerly HK, Zalutsky MR. N-Succinimidyl guanidinomethyl iodobenzoate protein radiohalogenation agents: influence of isomeric substitution on radiolabeling and target cell residualization. Nucl Med Biol. 2014;41(10):802–812.
Journal cover image

Published In

Nucl Med Biol

DOI

EISSN

1872-9614

Publication Date

2014

Volume

41

Issue

10

Start / End Page

802 / 812

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Tissue Distribution
  • Stereoisomerism
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Radiopharmaceuticals
  • Radionuclide Imaging
  • Nuclear Medicine & Medical Imaging
  • Mice
  • Isotope Labeling