Preclinical Evaluation of a Near-Infrared Labelled Antibody Targeting the Tumour Associated Xenoantigen N-Glycolyl-Neuraminic Acid GM3 Ganglioside
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".