The Use of Panitumumab-IRDye800CW in a Novel Murine Model for Conjunctival Squamous Cell Carcinoma

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Abstract

Purpose

Conjunctival squamous cell carcinoma (SCC) is a sight-threatening ocular surface malignancy with the primary treatment modality being surgical resection. To evaluate surgical imaging modalities to improve surgical resection, we established a novel murine model for conjunctival SCC to demonstrate the utility of panitumumab-IRDye800, a fluorescently labeled anti-epidermal growth factor receptor (EGFR) antibody.

Methods

NOD-scid IL2Rgamma ^null (NSG) mice received subconjunctival injection of UM-SCC-1 or SCC-9, head and neck SCC cell lines. On tumor growth, mice were injected with Panitumumab-IRDye800CW, and imaged with a small animal imaging system and optical coherence tomography (OCT). Immunohistochemistry for SCC markers were used to confirm tumor origin.

Results

Seventy-five percent (N = 4) of the UM-SCC-1 group developed aggressive, rapidly growing tumors that were P40 and EGFR positive within two weeks of inoculation. The SCC-9 tumors failed to demonstrate any growth (N = 4). Ocular tumors demonstrated high fluorescence levels with a tumor to background ratio of 3.8.

Conclusions

Subconjunctival injections are an appropriate technique to create in vivo models for assessing treatment modalities and novel therapies in conjunctival SCC.

Translational Relevance

This model demonstrates Panitumumab-IRDye800CW's utility in the ophthalmic setting and suggests that clinical trials may be warranted.

Related collections

Most cited references 35

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Determination of Tumor Margins with Surgical Specimen Mapping Using Near-Infrared Fluorescence

Rebecca Gao, Nutte Teraphongphom, Nynke van den Berg … (2018)

For many solid tumors, surgical resection remains the gold standard and tumor-involved margins are associated with poor clinical outcomes. Near-infrared (NIR) fluorescence imaging using molecular agents has shown promise for in situ imaging during resection. However, for cancers with difficult imaging conditions, surgical value may lie in tumor-mapping of surgical specimens. We thus evaluated a novel approach for real-time, intraoperative tumor margin assessment. 21 adult patients with biopsy-confirmed squamous cell carcinoma arising from the head and neck (HNSCC) scheduled for standard-of-care surgery were enrolled. Cohort 1 (n=3) received panitumumab-IRDye800CW at an intravenous microdose of 0.06 mg/kg, cohort 2A (n=5) received 0.5mg/kg, cohort 2B (n=7) received 1mg/kg, and cohort 3 (n=6) received 50 mg. Patients were followed 30 days post-infusion and adverse events were recorded. Imaging was performed using several closed- and wide-field devices. Fluorescence was histologically correlated to determine sensitivity and specificity. In situ imaging demonstrated tumor-to-background ratio (TBR) of 2-3, compared to ex vivo specimen imaging TBR of 5-6. We obtained clear differentiation between tumor and normal tissue, with a three-fold signal difference between positive and negative specimens (p<0.05). We achieved high correlation of fluorescence intensity with tumor location with sensitivities and specificities >89%; fluorescence predicted distance of tumor tissue to the cut surface of the specimen. This novel method of detecting tumor-involved margins in surgical specimens using a cancer-specific agent provides highly sensitive and specific, real-time, intraoperative surgical navigation in resections with complex anatomy which are otherwise less amenable to image guidance.

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Tumors of the conjunctiva and cornea.

Carol L. Shields, Jerry Shields (2015)

Tumors of the conjunctiva and cornea comprise a large and varied spectrum of conditions. These tumors are grouped into two major categories of congenital and acquired lesions. The acquired lesions are further subdivided based on origin of the mass into surface epithelial, melanocytic, vascular, fibrous, neural, histiocytic, myxoid, myogenic, lipomatous, lymphoid, leukemic, metastatic and secondary tumors. Melanocytic lesions include nevus, racial melanosis, primary acquired melanosis, melanoma, and other ocular surface conditions like ocular melanocytosis and secondary pigmentary deposition. The most frequent nonmelanocytic neoplastic lesions include squamous cell carcinoma and lymphoma, both of which have typical features appreciated on clinical examination. The caruncle displays a slightly different array of tumors compared to those elsewhere on the conjunctiva, as nevus and papilloma are most common, but oncocytoma and sebaceous gland hyperplasia, adenoma, and carcinoma can be found. In this report, we provide clinical description and illustration of the many conjunctival and corneal tumors and we discuss tumor management.

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Is Open Access

Color attributes, betacyanin, and carotenoid profiles, bioactive components, and radical quenching capacity in selected Amaranthus gangeticus leafy vegetables

Umakanta Sarker, Shinya Oba (2021)

Four selected A. gangeticus accessions were evaluated in terms of color attributes, phytopigments, including betaxanthin, betacyanin, and carotenoid profiles, proximate, minerals, and antioxidant capacity (AC). Color attributes, phytopigments, proximate, minerals, and AC of A. gangeticus significantly varied across the accessions. For the first time, we identified four betacyanin compounds, such as amaranthine, iso-amaranthine, betanin, iso-betanin. We also identified five carotenoid compounds zeaxanthin neoxanthin, violaxanthin, lutein, and pro-vitamin A in A. gangeticus accessions. A. gangeticus contained adequate carbohydrates, protein, moisture, and dietary fiber. We found adequate iron, manganese, copper, zinc, sodium, molybdenum, boron, potassium, calcium, magnesium, phosphorus, sulfur in A. gangeticus accessions. The accessions LS7 and LS9 had considerable color attributes, betacyanin, and carotenoid compounds, proximate, nutraceuticals, betalain, betaxanthin, and AC that could be used as preferable potent antioxidant varieties for consumption as sources of phytopigments, nutraceuticals, and antioxidants. The correlation study revealed that antioxidant constituents of A. gangeticus accession were strongly associated with AC. The identified components of betacyanin and carotenoid in A. gangeticus demands detail pharmacological study. The baseline data on color attributes, betacyanin, and carotenoid profiles, betaxanthins, betalains, and AC obtained in this present study could contribute to the scientific evaluation of pharmacologically active principles in A. gangeticus .

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Author and article information

Journal

Journal ID (nlm-ta): Transl Vis Sci Technol

Journal ID (iso-abbrev): Transl Vis Sci Technol

Journal ID (publisher-id): TVST

Title: Translational Vision Science & Technology

Publisher: The Association for Research in Vision and Ophthalmology

ISSN (Electronic): 2164-2591

Publication date (Electronic): 27 July 2022

Publication date Collection: July 2022

Volume: 11

Issue: 7

Electronic Location Identifier: 23

Affiliations

[1 ]Stanford University School of Medicine, Stanford, CA, USA

[2 ]Department of Ophthalmology, Stanford University School of Medicine, Stanford, CA, USA

[3 ]Trinity College of Arts and Sciences, Duke University, Durham, NC, USA

[4 ]Department of Otolaryngology–Head and Neck Surgery, Stanford Hospital and Clinics, Stanford, CA, USA

[5 ]Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA

[6 ]Department of Otolaryngology–Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, TN, USA

Author notes

[* ] Correspondence: Albert Y. Wu, Department of Ophthalmology, Stanford University School of Medicine, Stanford, CA, USA. e-mail: awu1@ 123456stanford.edu

Article

Publisher ID: TVST-22-4649

DOI: 10.1167/tvst.11.7.23

PMC ID: 9344218

PubMed ID: 35895055

SO-VID: aa3bcdfd-6baa-47d7-ab3b-df5cc6b9ff11

License:

This work is licensed under a Creative Commons Attribution 4.0 International License.

History

Date accepted : 19 June 2022

Date received : 30 March 2022

Page count

Pages: 10