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Fluorescence-guided resection of tumors in mouse models of oral cancer.

ABSTRACT: Complete removal and negative margins are the goal of any surgical resection of primary oral cavity carcinoma. Current approaches to determine tumor boundaries rely heavily on surgeons' expertise, and final histopathological reports are usually only available days after surgery, precluding contemporaneous re-assessment of positive margins. Intraoperative optical imaging could address this unmet clinical need. Using mouse models of oral cavity carcinoma, we demonstrated that PARPi-FL, a fluorescent PARP inhibitor targeting the enzyme PARP1/2, can delineate oral cancer and accurately identify positive margins, both macroscopically and at cellular resolution. PARPi-FL also allowed identification of compromised margins based on fluorescence hotspots, which were not seen in margin-negative resections and control tongues. PARPi-FL was further able to differentiate tumor from low-grade dysplasia. Intravenous injection of PARPi-FL has significant potential for clinical translation and could aid surgeons in assessing oral cancer margins in vivo.

SUBMITTER: Demetrio de Souza Franca P

PROVIDER: S-EPMC7341853 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Fluorescence-guided resection of tumors in mouse models of oral cancer.

Demétrio de Souza França Paula P Guru Navjot N Roberts Sheryl S Kossatz Susanne S Mason Christian C Abrahão Marcio M Ghossein Ronald A RA Patel Snehal G SG Reiner Thomas T

Scientific reports 20200707 1

Complete removal and negative margins are the goal of any surgical resection of primary oral cavity carcinoma. Current approaches to determine tumor boundaries rely heavily on surgeons' expertise, and final histopathological reports are usually only available days after surgery, precluding contemporaneous re-assessment of positive margins. Intraoperative optical imaging could address this unmet clinical need. Using mouse models of oral cavity carcinoma, we demonstrated that PARPi-FL, a fluoresce ...[more]

PMID: 32636416

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Project description:The standard treatment for glioblastoma multiforme (GBM) remains maximal safe surgical resection. Here, we evaluated the ability of a systemically administered antibody-dye probe conjugate (cetuximab-IRDye 800CW) to provide sufficient fluorescent contrast for surgical resection of disease in both subcutaneous and orthotopic animal models of GBM. Multiple luciferase-positive GBM cell lines (D-54MG, U-87MG, and U-251MG; n = 5) were implanted in mouse flank and tumors were fluorescently imaged daily using a closed-field near-infrared (NIR) system after cetuximab-IRDye 800CW systemic administration. Orthotopic models were also generated (n = 5), and tumor resection was performed under white light and fluorescence guidance using an FDA-approved wide-field NIR imaging system. Residual tumor was monitored using luciferase imaging. Immunohistochemistry was performed to characterize tumor fluorescence, epidermal growth factor receptor (EGFR) expression, and vessel density. Daily imaging of tumors revealed an average tumor-to-background (TBR) of 4.5 for U-87MG, 4.1 for D-54MG, and 3.7 for U-251MG. Fluorescence intensity within the tumors peaked on day-1 after cetuximab-IRDye 800CW administration, however the TBR increased over time in two of the three cell lines. For the orthotopic model, TBR on surgery day ranged from 19 to 23 during wide-field, intraoperative imaging. Surgical resection under white light on day 3 after cetuximab-IRDye 800CW resulted in an average 41% reduction in luciferase signal while fluorescence-guided resection using wide-field NIR imaging resulted in a significantly (P = 0.001) greater reduction in luciferase signal (87%). Reduction of luciferase signal was found to correlate (R (2) = 0.99) with reduction in fluorescence intensity. Fluorescence intensity was found to correlate (P < 0.05) with EGFR expression in D-54MG and U-251MG tumor types but not U-87MG. However, tumor fluorescence was found to correlate with vessel density for the U-87MG tumors. Here we show systemic administration of cetuximab-IRDye 800CW in combination with wide-field NIR imaging provided robust and specific fluorescence contrast for successful localization of disease in subcutaneous and orthotopic animal models of GBM.

Dataset Information

Fluorescence-guided resection of tumors in mouse models of oral cancer.

Publications

Fluorescence-guided resection of tumors in mouse models of oral cancer.

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