Dataset Information

Targeted Polymer-Based Probes for Fluorescence Guided Visualization and Potential Surgery of EGFR-Positive Head-and-Neck Tumors.

ABSTRACT: This report describes the design, synthesis and evaluation of tumor-targeted polymer probes to visualize epidermal growth factor receptor (EGFR)-positive malignant tumors for successful resection via fluorescence guided endoscopic surgery. Fluorescent polymer probes of various molecular weights enabling passive accumulation in tumors via enhanced permeability and retention were prepared and evaluated, showing an optimal molecular weight of 200,000 g/mol for passive tumor targeting. Moreover, poly(N-(2-hydroxypropyl)methacrylamide)-based copolymers labeled with fluorescent dyes were targeted with the EGFR-binding oligopeptide GE-11 (YHWYGYTPQNVI), human EGF or anti-EGFR monoclonal antibody cetuximab were all able to actively target the surface of EGFR-positive tumor cells. Nanoprobes targeted with GE-11 and cetuximab showed the best targeting profile but differed in their tumor accumulation kinetics. Cetuximab increased tumor accumulation after 15 min, whereas GE 11 needed at least 4 h. Interestingly, after 4 h, there were no significant differences in tumor targeting, indicating the potential of oligopeptide targeting for fluorescence-navigated surgery. In conclusion, fluorescent polymer probes targeted by oligopeptide GE-11 or whole antibody are excellent tools for surgical navigation during oncological surgery of head and neck squamous cell carcinoma, due to their relatively simple design, synthesis and cost, as well as optimal pharmacokinetics and accumulation in tumors.

SUBMITTER: Pola R

PROVIDER: S-EPMC7022460 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Targeted Polymer-Based Probes for Fluorescence Guided Visualization and Potential Surgery of EGFR-Positive Head-and-Neck Tumors.

Pola Robert R Böhmová Eliška E Filipová Marcela M Pechar Michal M Pankrác Jan J Větvička David D Olejár Tomáš T Kabešová Martina M Poučková Pavla P Šefc Luděk L Zábrodský Michal M Janoušková Olga O Bouček Jan J Etrych Tomáš T

Pharmaceutics 20200101 1

This report describes the design, synthesis and evaluation of tumor-targeted polymer probes to visualize epidermal growth factor receptor (EGFR)-positive malignant tumors for successful resection via fluorescence guided endoscopic surgery. Fluorescent polymer probes of various molecular weights enabling passive accumulation in tumors via enhanced permeability and retention were prepared and evaluated, showing an optimal molecular weight of 200,000 g/mol for passive tumor targeting. Moreover, pol ...[more]

PMID: 31906300

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Project description:BackgroundFluorescence molecular imaging using ABY-029, an epidermal growth factor receptor (EGFR)-targeted, synthetic Affibody peptide labeled with a near-infrared fluorophore, is under investigation for surgical guidance during head and neck squamous cell carcinoma (HNSCC) resection. However, tumor-to-normal tissue contrast is confounded by intrinsic physiological limitations of heterogeneous EGFR expression and non-specific agent uptake.ObjectiveIn this preliminary study, radiomic analysis was applied to optical ABY-029 fluorescence image data for HNSCC tissue classification through an approach termed "optomics." Optomics was employed to improve tumor identification by leveraging textural pattern differences in EGFR expression conveyed by fluorescence. The study objective was to compare the performance of conventional fluorescence intensity thresholding and optomics for binary classification of malignant vs. non-malignant HNSCC tissues.Materials and methodsFluorescence image data collected through a Phase 0 clinical trial of ABY-029 involved a total of 20,073 sub-image patches (size of 1.8 × 1.8 mm2) extracted from 24 bread-loafed slices of HNSCC surgical resections originating from 12 patients who were stratified into three dose groups (30, 90, and 171 nanomoles). Each dose group was randomly partitioned on the specimen-level 75%/25% into training/testing sets, then all training and testing sets were aggregated. A total of 1,472 standardized radiomic features were extracted from each patch and evaluated by minimum redundancy maximum relevance feature selection, and 25 top-ranked features were used to train a support vector machine (SVM) classifier. Predictive performance of the SVM classifier was compared to fluorescence intensity thresholding for classifying testing set image patches with histologically confirmed malignancy status.ResultsOptomics provided consistent improvement in prediction accuracy and false positive rate (FPR) and similar false negative rate (FNR) on all testing set slices, irrespective of dose, compared to fluorescence intensity thresholding (mean accuracies of 89% vs. 81%, P = 0.0072; mean FPRs of 12% vs. 21%, P = 0.0035; and mean FNRs of 13% vs. 17%, P = 0.35).ConclusionsOptomics outperformed conventional fluorescence intensity thresholding for tumor identification using sub-image patches as the unit of analysis. Optomics mitigate diagnostic uncertainties introduced through physiological variability, imaging agent dose, and inter-specimen biases of fluorescence molecular imaging by probing textural image information. This preliminary study provides a proof-of-concept that applying radiomics to fluorescence molecular imaging data offers a promising image analysis technique for cancer detection in fluorescence-guided surgery.

Dataset Information

Targeted Polymer-Based Probes for Fluorescence Guided Visualization and Potential Surgery of EGFR-Positive Head-and-Neck Tumors.

Publications

Targeted Polymer-Based Probes for Fluorescence Guided Visualization and Potential Surgery of EGFR-Positive Head-and-Neck Tumors.

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