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Purpose <p>Targeted and broadly applicable molecular targets are important for image guided surgery. Xenoantigens represent a particularly interesting class of targets. This study evaluates the xenoantigen N-glycolyl-neuraminic acid GM3 ganglioside (Neu5Gc-GM3) as a potential fluorescence-guided surgical tool.</p> Procedures <p>The antibody 14F7hT is conjugated to the near-infrared dye (IRDye800CW) and characterized under GLP conditions. The quality and stability of the 14F7hT-IRDye800CW probe was assessed. In vivo imaging using 14F7hT-IRDye800CW in mice with Neu5Gc GM3 positive and negative xenografts were compared to a control IgG-IRDye800CW probe targeting an epitope not present on the xenografts. Biodistribution, pharmacokinetics, and toxicity were evaluated.</p> Results <p>The 14F7hT-IRDye800CW probe was 98 ± 2% pure as determined by micro-capillary electrophoresis. The KDapp as determined by binding cell-lines expressing the target was unchanged after conjugation. We demonstrate a peak accumulation window of 12 – 48&#xa0;h in murine xenografts with male and female CD-1 nude mice administered 0.5 nmoles of the probe (i.v.) and very low uptake in other tissues. Preclinical toxicity studies in male and female balb/c mice support a no observed adverse effect level (NOAEL) of 50&#xa0;mg/kg in mice.</p> Conclusions <p>The 14F7hT-IRDye800CW probe was found to be safe and have low non-specific uptake in a model organism known to express the target. These data support future clinical development of the probe.</p>

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Preclinical Evaluation of a Near-Infrared Labelled Antibody Targeting the Tumour Associated Xenoantigen N-Glycolyl-Neuraminic Acid GM3 Ganglioside

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月17日

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  • Kris Barreto,
  • Wendy Bernhard,
  • Darien Toledo,
  • Kimberly Jett,
  • Angel Casaco,
  • Kalet León,
  • C. Ronald Geyer

摘要

Purpose

Targeted and broadly applicable molecular targets are important for image guided surgery. Xenoantigens represent a particularly interesting class of targets. This study evaluates the xenoantigen N-glycolyl-neuraminic acid GM3 ganglioside (Neu5Gc-GM3) as a potential fluorescence-guided surgical tool.

Procedures

The antibody 14F7hT is conjugated to the near-infrared dye (IRDye800CW) and characterized under GLP conditions. The quality and stability of the 14F7hT-IRDye800CW probe was assessed. In vivo imaging using 14F7hT-IRDye800CW in mice with Neu5Gc GM3 positive and negative xenografts were compared to a control IgG-IRDye800CW probe targeting an epitope not present on the xenografts. Biodistribution, pharmacokinetics, and toxicity were evaluated.

Results

The 14F7hT-IRDye800CW probe was 98 ± 2% pure as determined by micro-capillary electrophoresis. The KDapp as determined by binding cell-lines expressing the target was unchanged after conjugation. We demonstrate a peak accumulation window of 12 – 48 h in murine xenografts with male and female CD-1 nude mice administered 0.5 nmoles of the probe (i.v.) and very low uptake in other tissues. Preclinical toxicity studies in male and female balb/c mice support a no observed adverse effect level (NOAEL) of 50 mg/kg in mice.

Conclusions

The 14F7hT-IRDye800CW probe was found to be safe and have low non-specific uptake in a model organism known to express the target. These data support future clinical development of the probe.